Faculty Profiles - WADA Jun

Papers - WADA Jun

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Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells

Yoshihiko Itoh, Kenichi Inagaki, Tomohiro Terasaka, Eisaku Morimoto, Takahiro Ishii, Kimitomo Yamaoka, Satoshi Fujisawa, Jun Wada

International Journal of Molecular Sciences 2025.7

Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes

Naoko Nishii, Tomoko Kawai, Hiroki Yasuoka, Tadashi Abe, Nanami Tatsumi, Yuika Harada, Takaaki Miyaji, Shunai Li, Moemi Tsukano, Masami Watanabe, Daisuke Ogawa, Jun Wada, Kohji Takei, Hiroshi Yamada

International Journal of Molecular Sciences 2025.3

Supplement-induced acute kidney injury reproduced in kidney organoids

Hiroyuki Nakanoh, Kenji Tsuji, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada

American Journal of Nephrology 2025.2

Noncoding RNAs and diabetic kidney disease Reviewed

Jun Wada

Journal of Diabetes Investigation 2025.1

The Gut–Kidney Axis in Chronic Kidney Diseases

Kenji Tsuji, Naruhiko Uchida, Hiroyuki Nakanoh, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada

Diagnostics 2024.12

Characteristics of diabetes mellitus patients with nonviral chronic liver disease who developed hepatocellular carcinoma. Reviewed International journal

Kyo Sasaki, Miwa Kawanaka, Yasuyuki Tomiyama, Akinobu Takaki, Motoyuki Otsuka, Fusao Ikeda, Naoko Yoshioka, Hideaki Kaneto, Jun Wada, Tetsuya Fukuda, Keisuke Hino, Sohji Nishina

Hepatology research : the official journal of the Japan Society of Hepatology 2024.10

Language：English Publishing type：Research paper (scientific journal)

AIM: Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease. METHOD: Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. The clinical and laboratory parameters of patients with and without HCC were compared. RESULTS: Age ≥65 years, alcohol intake, lack of hepatic steatosis, triglyceride level <111 mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5 ng/mL, and des-γ-carboxy prothrombin concentration ≥26 mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p < 0.001) was associated with HCC development in patients aged <65 years, and medication for diabetes mellitus (OR 5.72, p = 0.001), lack of hepatic steatosis (OR 4.47, p = 0.002), lactate dehydrogenase ≥198 IU/L (OR 2.751, p = 0.031), M2BPGi ≥1.18 COI (OR 9.05, p < 0.001), and FIB-4 index ≥2.59 (OR 3.22, p = 0.017) were associated with HCC development in patients aged ≥65 years. CONCLUSIONS: In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging.

DOI： 10.1111/hepr.14124

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A case of renal hypouricemia due to T217M mutation in SLC22A12 incidentally associated with IgA nephropathy. Reviewed International journal

Yoshimasa Sakurabu, Haruhito A Uchida, Toshihisa Tahara, Tomohiko Asakawa, Haruka Yamasaki, Katsuyoshi Katayama, Shugo Okamoto, Yasuhiro Onishi, Natsumi Matsuoka-Uchiyama, Keiko Tanaka, Hidemi Takeuchi, Kenji Tsuji, Ryoko Umebayashi, Yuki Ohashi, Kimiyoshi Ichida, Jun Wada

Clinical case reports 12 ( 9 ) e9368 2024.9

Language：English Publishing type：Research paper (scientific journal)

A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events.

DOI： 10.1002/ccr3.9368

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Guidelines for clinical evaluation of chronic kidney disease in early stages : AMED research on regulatory science of pharmaceuticals and medical devices. Reviewed

Yuka Sugawara, Eiichiro Kanda, Takayuki Hamano, Seiji Itano, Hirokazu Okada, Koji Tomori, Yusuke Watanabe, Wataru Asakura, Yoshitaka Isaka, Kunitoshi Iseki, Tomoko Usui, Yusuke Suzuki, Mototsugu Tanaka, Rimei Nishimura, Kei Fukami, Kunihiro Matsushita, Jun Wada, Hirotaka Watada, Kohjiro Ueki, Naoki Kashihara, Masaomi Nangaku

Clinical and experimental nephrology 28 ( 9 ) 847 - 865 2024.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients. METHODS: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal. RESULTS: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review. CONCLUSION: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

DOI： 10.1007/s10157-024-02514-6

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Factors influencing the efficacy and safety of esaxerenone in hypertensive patients: a pooled analysis of five clinical studies on different comorbidities. Reviewed International journal

Kazuomi Kario, Tomohiro Katsuya, Jun Wada, Hirohiko Motoki, Koichiro Kuwahara, Kenichi Tsujita, Takashi Taguchi, Ayumi Tanabe, Tatsuo Shimosawa

Hypertension research : official journal of the Japanese Society of Hypertension 2024.8

Language：English Publishing type：Research paper (scientific journal)

This study aimed to identify factors associated with a strong home blood pressure (BP)-lowering effect of esaxerenone and the incidence of elevated serum potassium levels in hypertensive patients treated with esaxerenone. A pooled analysis of five multicenter, prospective, open-label single-arm studies was conducted, including 479 patients in the full analysis set (FAS) and 492 patients in the safety analysis set. Multivariate linear regression analysis of morning home systolic BP (SBP) and diastolic BP (DBP) changes from baseline to Week 12 in the FAS (primary endpoint) showed that male sex (estimated change 4.37 mmHg), office pulse rate ≥100 beats/min (25.10 mmHg), and calcium channel blocker (CCB) use as a basal antihypertensive agent (4.53 mmHg) were significantly associated with a positive estimated change (weaker BP-lowering effect) in morning home SBP. CCB use (3.70 mmHg) was associated with a positive estimated change in morning home DBP. Urine albumin-to-creatinine ratio 30 to <300 mg/gCr (-4.13 mmHg) was significantly associated with a negative estimated change (stronger BP-lowering effect) in morning home SBP. Based on multivariate logistic regression analysis, elevated baseline serum potassium level (≥4.5 vs < 4.5 mEq/L, odds ratio 13.502) was significantly associated with a high incidence of serum potassium level ≥5.5 mEq/L after esaxerenone treatment. In conclusion, factors associated with a strong BP-lowering effect of esaxerenone were female sex and use of renin-angiotensin system inhibitors as a basal antihypertensive drug. Patients with baseline serum potassium levels ≥4.5 mEq/L had an increased risk of developing elevated serum potassium levels (≥5.5 mEq/L) after esaxerenone treatment.

DOI： 10.1038/s41440-024-01818-0

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Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease. Reviewed

Seiji Kishi, Takaya Nakashima, Tadahiro Goto, Hajime Nagasu, Craig R Brooks, Hirokazu Okada, Kouichi Tamura, Toshiaki Nakano, Ichiei Narita, Shoichi Maruyama, Yuichiro Yano, Takashi Yokoo, Takashi Wada, Jun Wada, Masaomi Nangaku, Naoki Kashihara

Clinical and experimental nephrology 28 ( 8 ) 784 - 792 2024.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex (J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

DOI： 10.1007/s10157-024-02486-7

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A case of membranous nephropathy complicated by Cronkhite-Canada syndrome successfully treated with mizoribine. Reviewed

Hiroyuki Nakanoh, Kenji Tsuji, Shiho Morimoto, Kazuhiko Fukushima, Masaya Iwamuro, Haruhito A Uchida, Jun Wada

CEN case reports 2024.7

Language：English Publishing type：Research paper (scientific journal)

Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic hamartomatous gastrointestinal polyposis, hair loss, nail atrophy, hyperpigmentation, and diarrhea. While the relationship between CCS and nephritis remains unclear, seven cases of nephritis complicated by CCS have been reported to date, all of which were membranous nephropathy (MN). A 57-year-old man presented with taste disturbance, hair loss, nail plate atrophy, skin pigmentation, and frequent diarrhea. Endoscopic findings showed multiple polyposis of the stomach and large intestine. Given the above, he was diagnosed with CCS. The symptoms gradually improved with prednisolone treatment, although urinary protein and hypoproteinemia appeared during the tapering of prednisolone. He was diagnosed with MN using a renal biopsy, and immunofluorescence microscopy with IgG subclass staining showed predominantly diffuse granular capillary wall staining of IgG4. The cause of secondary MN was not found, including malignant tumors. Nephrotic-range proteinuria persisted despite treatment with prednisolone and cyclosporine. Additional treatment with mizoribine resulted in incomplete remission type 1 of nephrotic syndrome, suggesting that mizoribine may be a treatment option for patients with CCS with steroid-resistant MN. Considering a high prevalence of hypoproteinemia due to chronic diarrhea and protein-losing enteropathy in patients with CCS, proteinuria might be overlooked; thus, follow-up urinalysis would be recommended in patients with CCS.

DOI： 10.1007/s13730-024-00908-9

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Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database. Reviewed International journal

Tomohiko Kanaoka, Hiromichi Wakui, Yuichiro Yano, Hajime Nagasu, Hiroshi Kanegae, Masaomi Nangaku, Yosuke Hirakawa, Naoki Nakagawa, Jun Wada, Kazuhiko Tsuruya, Toshiaki Nakano, Shoichi Maruyama, Takashi Wada, Masaaki Konishi, Takanori Nagahiro, Kunihiro Yamagata, Ichiei Narita, Motoko Yanagita, Yoshio Terada, Shinichi Araki, Masanori Emoto, Hirokazu Okada, Yoshitaka Isaka, Yusuke Suzuki, Takashi Yokoo, Hiromi Kataoka, Eiichiro Kanda, Naoki Kashihara, Kouichi Tamura

Diabetes, obesity & metabolism 26 ( 7 ) 2905 - 2914 2024.7

Language：English Publishing type：Research paper (scientific journal)

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = -0.609, p = .039; β = -2.298, p < .001; β = -0.936, p = .048; β = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

DOI： 10.1111/dom.15611

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Preventive effects of vasohibin-2-targeting peptide vaccine for diabetic nephropathy. Reviewed International journal

Yuri Nakashima, Katsuyuki Tanabe, Tomoyo Mifune, Takato Nakadoi, Hiroki Hayashi, Hironori Nakagami, Yasufumi Sato, Jun Wada

American journal of physiology. Renal physiology 326 ( 6 ) F1054-F1065 2024.6

Language：English Publishing type：Research paper (scientific journal)

Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 wk apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 wk after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db/db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation.NEW & NOTEWORTHY This study demonstrated preventive effects of VASH2-targeting peptide vaccine therapy on albuminuria and glomerular microinflammation in STZ-induced diabetic mouse model by inhibiting renal Angpt2 expression. The vaccination was also effective in db/db mice. The results highlight the importance of VASH2 in the pathogenesis of early-stage diabetic nephropathy and the practicability of anti-VASH2 strategy as a vaccine therapy.

DOI： 10.1152/ajprenal.00341.2023

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Effects of empagliflozin in patients with chronic kidney disease from Japan: exploratory analyses from EMPA-KIDNEY. Reviewed

Masaomi Nangaku, William G Herrington, Shinya Goto, Shoichi Maruyama, Naoki Kashihara, Kohjiro Ueki, Jun Wada, Hirotaka Watada, Eitaro Nakashima, Ryonfa Lee, Dan Massey, Kaitlin J Mayne, Aiko Tomita, Richard Haynes, Sibylle J Hauske, Takashi Kadowaki

Clinical and experimental nephrology 28 ( 6 ) 588 - 595 2024.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: EMPA-KIDNEY assessed the effects of empagliflozin 10 mg once daily vs. placebo in 6609 patients with chronic kidney disease (CKD) at risk of progression, including 612 participants from Japan. METHODS: Eligibility required an estimated glomerular filtration rate (eGFR) of ≥ 20 < 45; or ≥ 45 < 90 ml/min/1.73m2 with a urinary albumin-to-creatinine ratio (uACR) of ≥ 200 mg/g. The primary outcome was a composite of kidney disease progression (end-stage kidney disease, a sustained eGFR decline to < 10 ml/min/1.73m2 or ≥ 40% from randomization, or renal death) or cardiovascular death. In post-hoc analyses, we explored the effects of empagliflozin in participants from Japan vs. non-Japan regions, including additional models assessing whether differences in treatment effects between these regions could result from differences in baseline characteristics. RESULTS: Japanese participants had higher levels of albuminuria and eGFR than those from non-Japan regions. During a median of 2.0 year follow-up, a primary outcome occurred in 432 patients (13.1%) in the empagliflozin group and in 558 patients (16.9%) in the placebo group (hazard ratio [HR], 0.72, 95% confidence interval [95%CI] 0.64-0.82; P < 0.0001). Among the participants from non-Japan regions, there were 399 vs. 494 primary outcomes (0.75, 0.66-0.86), and 33 vs. 64 (0.49, 0.32-0.75; heterogeneity p = 0.06) in Japan. Results were similar when models explicitly considered treatment interactions with diabetes status, categories of eGFR/uACR, and recruitment in Japan (heterogeneity p = 0.08). Safety outcomes were broadly comparable between the two groups, and by Japanese status. CONCLUSIONS: Empagliflozin safely reduced the risk of "kidney disease progression or cardiovascular death" in patients with CKD, with consistent effects in participants from Japan.

DOI： 10.1007/s10157-024-02489-4

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Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3). Reviewed International journal

Asami Ueno, Yasuhiro Onishi, Koki Mise, Satoshi Yamaguchi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Haruhito A Uchida, Kenichi Shikata, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, Tomokazu Nunoue, Jun Wada

BMJ open diabetes research & care 12 ( 3 ) 2024.5

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. RESEARCH DESIGN AND METHODS: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. RESULTS: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. CONCLUSIONS: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD. TRIAL REGISTRATION NUMBER: UMIN000011525.

DOI： 10.1136/bmjdrc-2024-004237

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All three in one: it's a cohort, proteomics, and Mendelian randomization biomarker study. Reviewed International journal

Jun Wada

The Journal of clinical endocrinology and metabolism 2024.5

Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes. Reviewed International journal

Zannatun Nyma, Kaori Kitaoka, Yuichiro Yano, Hiroshi Kanegae, Nomin Bayaraa, Seiji Kishi, Hajime Nagasu, Toshiaki Nakano, Jun Wada, Shoichi Maruyama, Naoki Nakagawa, Kouichi Tamura, Takashi Yokoo, Motoko Yanagita, Ichiei Narita, Kunihiro Yamagata, Takashi Wada, Kazuhiko Tsuruya, Naoki Nakashima, Yoshitaka Isaka, Masaomi Nangaku, Naoki Kashihara, Hirokazu Okada

Scientific reports 14 ( 1 ) 11481 - 11481 2024.5

Language：English Publishing type：Research paper (scientific journal)

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0-5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.

DOI： 10.1038/s41598-024-62152-6

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A multicenter, open‐label, single‐arm trial of the long‐term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE‐02) Reviewed

Yushi Hirota, Yasumasa Kakei, Junta Imai, Hideki Katagiri, Ken Ebihara, Jun Wada, Junichi Suzuki, Tatsuhiko Urakami, Takashi Omori, Wataru Ogawa

Journal of Diabetes Investigation 15 ( 9 ) 1211 - 1219 2024.5

Language：English Publishing type：Research paper (scientific journal)

AIMS/INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment-refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single-arm trial (EMPIRE-01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE-02) that followed on from EMPIRE-01. MATERIALS AND METHODS: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE-01 trial participated in EMPIRE-02. RESULTS: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE-02. The improvement in mean values of glycemic parameters observed in EMPIRE-01 was not sustained in EMPIRE-02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE-02 after exclusion of this subject from analysis. CONCLUSIONS: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

DOI： 10.1111/jdi.14226

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GRP78 Contributes to the Beneficial Effects of SGLT2 Inhibitor on Proximal Tubular Cells in DKD Reviewed International journal

Atsuko Nakatsuka, Satoshi Yamaguchi, Jun Wada

Diabetes 73 ( 5 ) 763 - 779 2024.5

Language：English Publishing type：Research paper (scientific journal)

The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on kidney function are well-known; however, their molecular mechanisms are not fully understood. We focused on 78-kDa glucose-regulated protein (GRP78) and its interaction with SGLT2 and integrin-β1 beyond the chaperone property of GRP78. In streptozotocin (STZ)-induced diabetic mouse kidneys, GRP78, SGLT2, and integrin-β1 increased in the plasma membrane fraction, while they were suppressed by canagliflozin. The altered subcellular localization of GRP78/integrin-β1 in STZ mice promoted epithelial mesenchymal transition (EMT) and fibrosis, which were mitigated by canagliflozin. High-glucose conditions reduced intracellular GRP78, increased its secretion, and caused EMT-like changes in cultured HK2 cells, which were again inhibited by canagliflozin. Urinary GRP78 increased in STZ mice, and in vitro experiments with recombinant GRP78 suggested that inflammation spread to surrounding tubular cells and that canagliflozin reversed this effect. Under normal glucose culture, canagliflozin maintained sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) activity, promoted ER robustness, reduced ER stress response impairment, and protected proximal tubular cells. In conclusion, canagliflozin restored subcellular localization of GRP78, SGLT2, and integrin-β1 and inhibited EMT and fibrosis in DKD. In nondiabetic chronic kidney disease, canagliflozin promoted ER robustness by maintaining SERCA activity and preventing ER stress response failure, and it contributed to tubular protection.

DOI： 10.2337/db23-0581

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Renal outcomes with sodium‐glucose cotransporter 2 inhibitors in Japanese people with grade 3 chronic kidney disease and type 2 diabetes: Analysis of medical administrative databases Reviewed International journal

Hiroaki Iijima, Maki Gouda, Hideaki Hida, Kazumi Mori‐Anai, Akiko Takahashi, Ryoichi Minai, Hideki Ninomiya, Yoshiyuki Saito, Atsushi Miyawaki, Jun Wada

Diabetes, Obesity and Metabolism 26 ( 5 ) 1615 - 1623 2024.5

Language：English Publishing type：Research paper (scientific journal)

AIM: To evaluate whether sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy is associated with a reduction of renal events compared with other glucose-lowering drugs (oGLDs) among Japanese people with type 2 diabetes (T2D) and grade 3 (G3) chronic kidney disease (CKD) in a real-world clinical practice setting. MATERIALS AND METHODS: People with T2D who were newly prescribed an SGLT2i or an oGLD from April 2014 to November 2021 (without prior use of index drugs for ≥ 1 year prior to index date) and G3 CKD (estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m2) were selected from the Medical Data Vision database (MDV-DB) and the Real-World Data database (RWD-DB). SGLT2i and oGLD users were matched (1:1) using propensity score on patient background characteristics. The primary endpoint was a composite of the development of end-stage kidney disease or a sustained decline in eGFR of 50% or more. Hazard ratios (HRs) were estimated using the Cox proportional hazards model. RESULTS: Overall, 3190 (1595 per group) patients in the MDV-DB and 2572 (1286 per group) patients in the RWD-DB were included in the analyses. The composite outcome was significantly lower in the SGLT2i group than in the oGLD group in the MDV-DB (HR 0.49, 95% confidence interval [CI] 0.33 to 0.74, P < 0.001) and in the RWD-DB (HR 0.57, 95% CI 0.37 to 0.88, P = 0.011). CONCLUSIONS: Japanese people with T2D and G3 CKD initiating an SGLT2i had a lower risk of renal events than people initiating an oGLD.

DOI： 10.1111/dom.15461

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Successful treatment for life threatening recurrent non-traumatic rectus sheath hematoma in a case with microscopic polyangiitis with rapidly progressive glomerulonephritis. Reviewed

Hiroyuki Nakanoh, Hidemi Takeuchi, Morimoto Shiho, Yuya Terajima, Shugo Okamoto, Yasuhiro Onishi, Keiko Tanaka, Takayuki Katsuyama, Kenji Tsuji, Yoshinori Matsumoto, Katsuyuki Tanabe, Hiroshi Morinaga, Mayu Uka, Koji Tomita, Haruhito A Uchida, Takao Hiraki, Jun Wada

Internal medicine (Tokyo, Japan) 2024.4

Language：English Publishing type：Research paper (scientific journal)

A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.

DOI： 10.2169/internalmedicine.3239-23

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A Case of Pseudoxanthoma Elasticum with juvenile-onset hypertension. Reviewed

Katsuyoshi Katayama, Haruhito A Uchida, Aya Takehara, Jun Wada

Internal medicine (Tokyo, Japan) 2024.4

Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study. Reviewed

Hiroko Takahashi, Jun Eguchi, Mayu Watanabe, Masanori Nakayama, Jun Wada

Acta medica Okayama 78 ( 2 ) 185 - 191 2024.4

Language：English Publishing type：Research paper (scientific journal)

The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients.

DOI： 10.18926/AMO/66927

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Effects of HIF-PHD inhibitors in kidney development Reviewed International journal

Soichiro Haraguchi, Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

Nephrology Dialysis Transplantation 39 ( 8 ) 1368 - 1370 2024.3

The first presentation of a case of nail-patella syndrome newly diagnosed at the onset of rheumatoid arthritis: a case report. Reviewed International journal

Kazuya Matsumoto, Yoshinori Matsumoto, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Takayuki Katsuyama, Eri Katsuyama, Yoshihisa Nasu, Ken-Ei Sada, Jun Wada

BMC musculoskeletal disorders 25 ( 1 ) 139 - 139 2024.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal dominant disorder that is characterized by dysplasia of the nails, hypoplasia and/or dislocation of the patella and the presence of iliac horns. Using the CARE guidelines, we present the first reported case of NPS that was newly diagnosed at the onset of rheumatoid arthritis (RA). CASE PRESENTATION: A 74-year-old man was admitted to our hospital due to an 8-month history of arthralgia in bilateral wrists, elbows and fingers. He had a past history of glaucoma and left patella dislocation that had been operatively recentered at the age of 15 years. Laboratory data showed elevated levels of serum C-reactive protein and rheumatoid factor and an elevated titer of anti-SS-A antibodies, while estimated glomerular filtration rate (eGFR), titers of other antibodies and the results of a urinary test were normal. An X-ray showed deformity of bilateral radial heads and the right elbow, and magnetic resonance imaging (MRI) of his hands showed synovitis and erosion in the multiple swollen joints of the wrists and fingers. In addition to these typical features of RA, he had bilateral thumb nail dysplasia with mild hypoplasia of bilateral patellae and iliac horns as shown by the X-ray. He was diagnosed as having autosomal dominant disorder NPS co-existing with RA and he was treated with methotrexate in combination with an oral Janus kinase (JAK) inhibitor, leading to induction of remission. CONCLUSIONS: We have presented a rare case of NPS that was newly diagnosed at the onset of RA. Clinical and radiographic findings of NPS are highlighted in this case report for diagnosing NPS on the basis of typical manifestations.

DOI： 10.1186/s12891-024-07242-2

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A Multicenter, Open-Label, Single-Arm Trial of the Efficacy and Safety of Empagliflozin Treatment for Refractory Diabetes Mellitus with Insulin Resistance (EMPIRE-01). Reviewed International journal

Yushi Hirota, Yasumasa Kakei, Junta Imai, Hideki Katagiri, Ken Ebihara, Jun Wada, Junichi Suzuki, Tatsuhiko Urakami, Takashi Omori, Wataru Ogawa

Diabetes therapy : research, treatment and education of diabetes and related disorders 15 ( 2 ) 533 - 545 2024.2

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophic diabetes. METHODS: The trial was conducted at five academic centers in Japan and included seven patients with insulin resistance syndrome and one patient with lipoatrophic diabetes. Participants received 10 mg of empagliflozin daily. If the hemoglobin A1c (HbA1c) level was ≥ 7.0% (52 mmol/mol) after 12 weeks, the dose was adjusted to 25 mg. The study duration was 24 weeks, and the primary outcome was the change in HbA1c level by the end of the treatment period. Safety evaluations were performed for all participants. RESULTS: By the end of the 24-week treatment period, the mean HbA1c level for all eight patients had decreased by 0.99 percentage points (10.8 mmol/mol) (95% confidence interval [CI], 0.59 to 1.38 percentage points, 6.6 to 14.9 mmol/mol) and the mean fasting plasma glucose concentration had declined by 63.9 mg/dL (3.55 mmol/L) (95% CI 25.5 to 102.3 mg/dL, 1.42 to 5.68 mmol/L). Continuous glucose monitoring revealed a reduction in mean glucose levels from 164.3 ± 76.1 to 137.6 ± 46.6 mg/dL (9.13 ± 4.23 to 7.65 ± 2.59 mmol/L) as well as an increase in the time in range (70-180 mg/dL) from 58.9 ± 36.1% to 70.8 ± 18.3%. Seventeen mild adverse events were recorded in five individuals throughout the study period. No severe events were reported. The mean body mass showed a slight decrease and the mean serum ketone body concentration showed a slight increase during treatment. CONCLUSION: Our results demonstrate that empagliflozin shows a certain level of efficacy and safety for treatment of insulin resistance syndrome and lipoatrophic diabetes. TRIAL REGISTRATION: jRCTs2051190029 and NCT04018365.

DOI： 10.1007/s13300-023-01526-x

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Late-onset renal variant Fabry disease with R112H mutation and mild increase in plasma globotriaosylsphingosine: a case report. Reviewed International journal

Keiko Tanaka, Hitoshi Sugiyama, Hiroshi Morinaga, Akifumi Onishi, Katsuyuki Tanabe, Haruhito A Uchida, Hiroki Maruyama, Jun Wada

Frontiers in medicine 11 1383309 - 1383309 2024

Language：English Publishing type：Research paper (scientific journal)

Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.

DOI： 10.3389/fmed.2024.1383309

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Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes. Reviewed International journal

Yuzuki Kano, Satoshi Yamaguchi, Koki Mise, Chieko Kawakita, Yasuhiro Onishi, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Jun Wada

Kidney360 5 ( 2 ) 182 - 194 2023.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Inhibition of glucose influx into proximal tubular cells (PTCs) by sodium-glucose co-transporter 2 (SGLT2) inhibitors revealed prominent therapeutic impacts on diabetic kidney disease (DKD). Collectrin (CLTRN) serves as a chaperone for the trafficking of neutral amino acid transporters in the apical membranes of proximal tubular cells. We investigated the beneficial effects of reduced influx of amino acids into proximal tubular cells in diabetes and obesity model of Cltrn-/y mice. METHODS: Cltrn+/y and Cltrn-/y mice at 5 weeks of age were assigned to standard diet- (STD) and streptozotocin and high fat diet-treated (STZ-HFD) groups. RESULTS: At 22-23 weeks of age, body weight and HbA1c levels significantly increased in STZ-HFD-Cltrn+/y compared to STD-Cltrn+/y; however, they were not altered in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. At 20 weeks of age, urinary albumin creatinine ratio (UACR) was significantly reduced in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. Under the treatments with STZ and HFD, the Cltrn gene deficiency caused significant increase in urinary concentration of amino acids such as Gln, His, Gly, Thr, Tyr, Val, Trp, Phe, Ile, Leu and Pro. In proximal tubular cells in STZ-HFD-Cltrn+/y, the enlarged lysosomes with diameter of 10 μm or more were associated with reduced autolysosomes, and the formation of giant lysosomes was prominently suppressed in STZ-HFD-Cltrn-/y. Phospho-mTOR and inactive form of phospho-TFEB were reduced in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. CONCLUSIONS: The reduction of amino acids influx into proximal tubular cells inactivated mTOR, activated TFEB, improved lysosome function, and ameliorated vacuolar formation of PTCs in STZ-HFD-Cltrn-/y mice.

DOI： 10.34067/KID.0000000000000333

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Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study. Reviewed International journal

Kenji Tsuji, Hiroyuki Nakanoh, Kensaku Takahashi, Takafumi Morita, Yizhen Sang, Kazuhiko Fukushima, Natsumi Matsuoka-Uchiyama, Yasuhiro Onishi, Haruhito A Uchida, Shinji Kitamura, Jun Wada

Kidney medicine 5 ( 12 ) 100733 - 100733 2023.12

Language：English Publishing type：Research paper (scientific journal)

RATIONALE & OBJECTIVE: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled. PREDICTORS: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score. OUTCOMES: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy. ANALYTICAL APPROACH: Cox proportional hazards model. RESULTS: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91). LIMITATIONS: Single-center study and small sample size. CONCLUSIONS: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy. PLAIN-LANGUAGE SUMMARY: Assessment of kidney biopsies provides crucial information for diagnosis, disease activity, and prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system. Currently, the role of VMC in kidney health and diseases and the clinical significance of VMC variants are poorly understood. In the present study, we have shown that an infiltration of ≥80 inflammatory cells/mm2-VMC area (inflammatory-VMC) is independently associated with kidney disease progression after adjustments for known risk factors of progression. Therefore, assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.

DOI： 10.1016/j.xkme.2023.100733

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Preventive effect of culture supernatant of epithelial-like peritoneal mesothelial cells on peritoneal fibrosis. Reviewed International journal

Kensaku Takahashi, Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis 44 ( 3 ) 8968608231213577 - 8968608231213577 2023.11

Language：English Publishing type：Research paper (scientific journal)

Peritoneal fibrosis (PF) is a primary reason for discontinuing peritoneal dialysis, which involves characteristic changes of peritoneal mesothelial cells (PMCs). We previously reported preventive effects of implanting human epithelial-like PMCs (P-Epi) for mouse PF caused by mechanical peritoneum scrapings. In the present study, we analysed the preventive effects of culture supernatant of P-Epi in PF. Concentrated culture supernatant of P-Epi or human fibroblast-like PMCs (P-Fibro) or vehicles was injected into nude mice that had undergone mechanical scraping of the parietal and visceral peritoneum, and thickness and amount of adhesions were analysed. Although increased peritoneal adhesions and peritoneum thickening were observed in the vehicle-injected positive control group compared to the sham operation group, fewer number of adhesions and less thickness were observed in the mice treated with culture supernatant of P-Epi, but not P-Fibro, compared to the vehicle-injected positive controls. Immunofluorescent analysis revealed that the expression of extracellular matrix, type I collagen and fibronectin, was lower in the mice treated with culture supernatant of P-Epi than in the vehicle-injected positive controls. In addition, exosomes from P-Epi significantly reduced transforming growth factor-β (TGF-β)-induced expressions of type I collagen and fibronectin in 3T3 fibroblast cells. Collectively, culture supernatant of P-Epi has preventive effects on PF, thus cell therapy is not necessarily required. Further exploration of substances secreted by P-Epi and their protective mechanisms could lead to the development of therapeutic strategies to limit PF.

DOI： 10.1177/08968608231213577

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Neutrophil Elastase Inhibition by Sivelestat (ONO-5046) Attenuates AngII-induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice. Reviewed International journal

Yoshiko Hada, Haruhito A Uchida, Shugo Okamoto, Nozomu Otaka, Katsuyoshi Katayama, Venkateswaran Subramanian, Alan Daugherty, Jun Wada

American journal of hypertension 37 ( 5 ) 349 - 357 2023.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Abdominal aortic aneurysm (AAA) is an arterial disease characterized by dilatation of the aortic wall. It has been suggested that neutrophil counts and neutrophil elastase activity are associated with AAA. We investigated whether a neutrophil elastase (NE) inhibitor, sivelestat (Siv), had a protective effect against angiotensin II (AngII)-induced AAAs. METHODS: Male apolipoprotein E-deficient mice were assigned into 3 groups: Vehicle+saline, AngII+saline, and AngII+Siv. All mice were administered intraperitoneally with either Siv or vehicle twice daily after AngII infusion. RESULTS: In the 4-week AngII infusion study, plasma NE concentration (p=0.041) and its activity (p=0.011) were elevated by AngII. These increases were attenuated by Siv (concentration:p=0.010, activity:p=0.027). Further, plasma elastase activity was closely correlated with aortic width (R=0.6976, p<0.001). In the 1-week AngII infusion study, plasma and tissue elastase activity increased by AngII (plasma:p=0.034, tissue:p<0.001), but were reduced by Siv (plasma:p=0.014, tissue:p=0.024). AngII increased aortic width (p=0.011) but was attenuated by co-administration of Siv (p=0.022). Moreover, Siv decreased the incidence of AAAs (p=0.009). Elastin fragmentation induced by AngII was reduced by Siv. Many inflammatory cells that were either CD68 or Gr-1 positive were observed in the AngII+saline group, whereas few inflammatory cells were accumulated in the AngII+Siv group. MMP-2 and MMP-9 were enhanced by AngII, but were reduced by Siv. In vitro, MMP-2 activity was induced by human NE (medium:p<0.001, cells:p=0.001), which was attenuated by co-incubation of Siv in medium (p<0.001) and protein of human aortic smooth muscle cells (p=0.001). CONCLUSION: Siv attenuated AngII-induced AAA through the inhibition of NE.

DOI： 10.1093/ajh/hpad107

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Infliximab biosimilar-induced lupus nephritis: A case report. Reviewed International journal

Kenta Shidahara, Takayuki Katsuyama, Kei Hirose, Kazuya Matsumoto, Shoichi Nawachi, Takato Nakadoi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Eri Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

Modern rheumatology case reports 8 ( 1 ) 74 - 76 2023.10

Language：English Publishing type：Research paper (scientific journal)

We present a case of microhematuria, proteinuria and hypocomplementemia that developed in a 55-year-old female who was being treated with an infliximab biosimilar (IFX-BS) for rheumatoid arthritis (RA). Renal biopsy showed lupus nephritis (ISN/RPS classification class IV+V). Treatment with the IFX-BS was discontinued, and treatment with prednisolone, hydroxychloroquine and abatacept was started, resulting in clinical remission of lupus nephritis and RA. Although tumor necrosis factor-α (TNF-α) inhibitors are known to induce production of autoantibodies, symptoms are usually limited to skin involvement or arthritis, and renal complications are rare. Physicians should be aware of the risk of lupus nephritis and carefully monitor patients for the development of renal involvement during treatment with TNF-α inhibitors.

DOI： 10.1093/mrcr/rxad061

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Kidney outcomes associated with haematuria and proteinuria trajectories among patients with IgA nephropathy in real-world clinical practice: The Japan Chronic Kidney Disease Database. Reviewed International journal

Yuichiro Yano, Hajime Nagasu, Hiroshi Kanegae, Masaomi Nangaku, Yosuke Hirakawa, Yuka Sugawara, Naoki Nakagawa, Jun Wada, Hitoshi Sugiyama, Toshiaki Nakano, Takashi Wada, Miho Shimizu, Hitoshi Suzuki, Hiroyuki Komatsu, Naoki Nakashima, Kaori Kitaoka, Ichiei Narita, Hirokazu Okada, Yusuke Suzuki, Naoki Kashihara

Nephrology (Carlton, Vic.) 29 ( 2 ) 65 - 75 2023.10

Language：English Publishing type：Research paper (scientific journal)

AIM: Among patients with Immunoglobulin A (IgA) nephropathy, we aimed to identify trajectory patterns stratified by the magnitude of haematuria and proteinuria using repeated urine dipstick tests, and assess whether the trajectories were associated with kidney events. METHODS: Using a nationwide multicentre chronic kidney disease (CKD) registry, we analysed data from 889 patients with IgA nephropathy (mean age 49.3 years). The primary outcome was a sustained reduction in eGFR of 50% or more from the index date and thereafter. During follow-up (median 49.0 months), we identified four trajectories (low-stable, moderate-decreasing, moderate-stable, and high-stable) in both urine dipstick haematuria and proteinuria measurements, respectively. RESULTS: In haematuria trajectory analyses, compared to the low-stable group, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) for kidney events were 2.59 (95% CI, 1.48-4.51) for the high-stable, 2.31 (95% CI, 1.19-4.50) for the moderate-stable, and 1.43 (95% CI, (0.72-2.82) for the moderate-decreasing groups, respectively. When each proteinuria trajectory group was subcategorized according to haematuria trajectories, the proteinuria group with high-stable and with modest-stable haematuria trajectories had approximately 2-times higher risk for eGFR reduction ≥50% compared to that with low-stable haematuria trajectory. CONCLUSION: Assessments of both haematuria and proteinuria trajectories using urine dipstick could identify high-risk IgA nephropathy patients.

DOI： 10.1111/nep.14250

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Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes. Reviewed

Naoko Kurooka, Jun Eguchi, Jun Wada

Journal of diabetes investigation 14 ( 10 ) 1148 - 1156 2023.10

Language：English Publishing type：Research paper (scientific journal)

In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.

DOI： 10.1111/jdi.14056

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Role of Semaphorin 3A in Kidney Development and Diseases. Reviewed International journal

Yizhen Sang, Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

Diagnostics (Basel, Switzerland) 13 ( 19 ) 2023.9

Language：English Publishing type：Research paper (scientific journal)

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases.

DOI： 10.3390/diagnostics13193038

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MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury. Reviewed International journal

Kenji Tsuji, Hiroyuki Nakanoh, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

Diagnostics (Basel, Switzerland) 13 ( 18 ) 2023.9

Language：English Publishing type：Research paper (scientific journal)

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

DOI： 10.3390/diagnostics13182893

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The Association of Grit With Burnout Components (Professional Efficacy, Exhaustion, and Cynicism) Among Academic Rheumatologists: The TRUMP 2 -SLE Study. Reviewed International journal

Yoshia Miyawaki, Ken-Ei Sada, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Keigo Hayashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nao Oguro, Nobuyuki Yajima, Yuichi Ishikawa, Natsuki Sakurai, Chiharu Hidekawa, Ryusuke Yoshimi, Takanori Ichikawa, Dai Kishida, Yasuhiro Shimojima, Jun Wada, Noriaki Kurita

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 29 ( 6 ) 268 - 274 2023.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists. METHODS: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [assistant professor or higher vs lower], marital status, and having children). RESULTS: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04). CONCLUSIONS: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit.

DOI： 10.1097/RHU.0000000000001989

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Pharmacologic inhibition of PARP5, but not that of PARP1 or 2, promotes cytokine production and osteoclastogenesis through different pathways. Reviewed International journal

Yosuke Asano, Yoshinori Matsumoto, Fang He, Takayuki Katsuyama, Eri Katsuyama, Shigetomo Tsuji, Hiroshi Kamioka, Jose La Rose, Robert Rottapel, Jun Wada

Clinical and experimental rheumatology 41 ( 9 ) 1735 - 1745 2023.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: PARPs, which are members of the poly(ADP-ribose) polymerase superfamily, promote tumorigenesis and tumour-associated inflammation and are thus therapeutic targets for several cancers. The aim of the present study is to investigate the mechanistic insight into the roles PARPs for inflammation. METHODS: Primary murine macrophages were cultured in the presence or absence of the PARP5 inhibitor NVP-TNKS656 to examine the role of PARP5 for cytokine production. RESULTS: In contrast to the roles of other PARPs for induction of inflammation, we found in the present study that pharmacologic inhibition of PARP5 induces production of inflammatory cytokines in primary murine macrophages. We found that treatment with the PARP5 inhibitor NVP-TNKS656 in macrophages enhanced steady-state and LPS-mediated cytokine production through degradation of IκBα and subsequent nuclear translocation of NF-κB. We also found that pharmacologic inhibition of PARP5 stabilises the adaptor protein 3BP2, a substrate of PARP5, and that accelerated cytokine production induced by PARP5 inhibition was rescued in 3BP2-deleted macrophages. Additionally, we found that LPS increases the expression of 3BP2 and AXIN1, a negative regulator of β-catenin, through suppression of PARP5 transcripts in macrophages, leading to further activation of cytokine production and inhibition of β-catenin-mediated cell proliferation, respectively. Lastly, we found that PARP5 inhibition in macrophages promotes osteoclastogenesis through stabilisation of 3BP2 and AXIN1, leading to activation of SRC and suppression of β-catenin, respectively. CONCLUSIONS: Our results show that pharmacologic inhibition of PARP5 against cancers unexpectedly induces adverse autoinflammatory side effects through activation of innate immunity, unlike inhibition of other PARPs.

DOI： 10.55563/clinexprheumatol/qf55h8

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Urinary growth differentiation factor 15 predicts renal function decline in diabetic kidney disease. Reviewed International journal

Toma Oshita, Shun Watanabe, Takafumi Toyohara, Ryota Kujirai, Koichi Kikuchi, Takehiro Suzuki, Chitose Suzuki, Yotaro Matsumoto, Jun Wada, Yoshihisa Tomioka, Tetsuhiro Tanaka, Takaaki Abe

Scientific reports 13 ( 1 ) 12508 - 12508 2023.8

Language：English Publishing type：Research paper (scientific journal)

Sensitive biomarkers can enhance the diagnosis, prognosis, and surveillance of chronic kidney disease (CKD), such as diabetic kidney disease (DKD). Plasma growth differentiation factor 15 (GDF15) levels are a novel biomarker for mitochondria-associated diseases; however, it may not be a useful indicator for CKD as its levels increase with declining renal function. This study explores urinary GDF15's potential as a marker for CKD. The plasma and urinary GDF15 as well as 15 uremic toxins were measured in 103 patients with CKD. The relationship between the urinary GDF15-creatinine ratio and the uremic toxins and other clinical characteristics was investigated. Urinary GDF15-creatinine ratios were less related to renal function and uremic toxin levels compared to plasma GDF15. Additionally, the ratios were significantly higher in patients with CKD patients with diabetes (p = 0.0012) and reduced with statin treatment. In a different retrospective DKD cohort study (U-CARE, n = 342), multiple and logistic regression analyses revealed that the baseline urinary GDF15-creatinine ratios predicted a decline in estimated glomerular filtration rate (eGFR) over 2 years. Compared to the plasma GDF15 level, the urinary GDF15-creatinine ratio is less dependent on renal function and sensitively fluctuates with diabetes and statin treatment. It may serve as a good prognostic marker for renal function decline in patients with DKD similar to the urine albumin-creatinine ratio.

DOI： 10.1038/s41598-023-39657-7

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Co-occurrence of Three Systemic Diseases: ANCA-associated Vasculitis, Sjögren's syndrome and Sarcoidosis. Reviewed

Kenji Tsuji, Yuka Okuyama, Yosuke Asano, Kimitomo Yamaoka, Shinji Kitamura, Jun Wada

Internal medicine (Tokyo, Japan) 62 ( 15 ) 2215 - 2221 2023.8

Language：English Publishing type：Research paper (scientific journal)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Sjögren's syndrome (SjS), and sarcoidosis are systemic diseases targeting multiple organs. While a careful differential diagnosis of these diseases is often required, their co-occurrence in the same patient has been previously reported. We herein report a 58-year-old Japanese man diagnosed with the co-occurrence of three systemic diseases (AAV, SjS, and sarcoidosis) in addition to monoclonal gammopathy of undetermined significance (MGUS), which emphasizes the importance of considering the possible co-occurrence of these diseases as well as their differentiation.

DOI： 10.2169/internalmedicine.0966-22

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Immunosuppressive Treatment for an anti-U1 Ribonucleoprotein Antibody-positive Patient with Pulmonary Arterial Hypertension: A Case Report. Reviewed

Kazuya Matsumoto, Yoshia Miyawaki, Takayuki Katsuyama, Takato Nakadoi, Kenta Shidahara, Kei Hirose, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Eri Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Atsushi Mori, Satoshi Akagi, Ken-Ei Sada, Jun Wada

Internal medicine (Tokyo, Japan) 63 ( 5 ) 671 - 676 2023.7

Language：English Publishing type：Research paper (scientific journal)

A 34-year-old woman with pulmonary arterial hypertension (PAH) was admitted to the hospital. She had been diagnosed with PAH three years earlier and treated with triple vasodilator therapy. She was positive for anti-U1 ribonucleoprotein antibodies but did not show any other symptoms associated with autoimmune diseases. Corticosteroid and cyclophosphamide therapy was administered, suspecting the involvement of immunological pathophysiology. After 3 weeks, the mean pulmonary artery pressure decreased from 50 to 38 mmHg without any change in the vasodilators. Immunosuppressive therapy was effective in this patient with PAH with an anti-U1 ribonucleoprotein-antibody-positive response and might be an option for patients with these specific features.

DOI： 10.2169/internalmedicine.1407-22

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Retroperitoneal Solid Pseudopapillary Tumor Mimicking Adrenal Malignant Tumor in a 67-Year-Old Man. Reviewed International journal

Takahiro Ishii, Tomohiro Terasaka, Kenji Nishida, Jun Wada

JCEM case reports 1 ( 4 ) luad090 2023.7

Language：English

Solid pseudopapillary tumor (SPT) is a low-grade malignant tumor of the pancreas. SPT typically affects women and can occur in ectopic pancreatic region; however, it also occurs rarely in retroperitoneum. The tumor may be bulky at the time of diagnosis since there is no specific clinical manifestation. Here we present an older male case with retroperitoneal SPT. A 67-year-old man consulted for intermittent fever and lumbago. His basal hormonal profile screened out a functional tumor. Computed tomography (CT) showed a gigantic mass in his left adrenal region. A normal left adrenal gland was not identified, and the tumor's feeding artery was recognized as the left adrenal artery by the contrast-enhanced CT. Adrenal malignant tumor was suspected, and tumor resection was performed. The resected tumor size was 15 × 10 × 9 cm. Histologically, epithelial-like cells with round nuclei and a small amount of eosinophilic cytoplasm proliferated in papillary (around the blood vessels) or uniformly solid form. By immunostaining, tumor cells were vimentin, CD56, cytokeratin AE1/AE3, CD10, β-catenin in the nucleus, cyclin D1, and PgR positive. These findings led to the diagnosis of SPT. Although rare, SPT should be considered as a differential diagnosis in cases of a mass arising from the adrenal region.

DOI： 10.1210/jcemcr/luad090

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NDUFS4 Regulates Cristae Remodeling in Diabetic Kidney Disease Reviewed International journal

Farhad Danesh, Koki Mise, Jianyin Long, Daniel Galvan, Zengchun Ye, Guizhen Fan, Irina Serysheva, Travis Moore, Jun Wada, Paul Schumacker, Benny Chang

Nature communications 15 ( 1 ) 1965 - 1965 2023.6

Language：English Publishing type：Research paper (scientific journal)

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that conditional male mice with genetic overexpression of Ndufs4 exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify the role of cristae shaping protein STOML2 in linking NDUFS4 with improved cristae morphology. Together, we provide the evidence on the central role of NDUFS4 as a regulator of cristae remodeling and mitochondrial function in kidney podocytes. We propose that targeting NDUFS4 represents a promising approach to slow the progression of DKD.

DOI： 10.21203/rs.3.rs-3070079/v1

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Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones. Reviewed

Yusuke Shibata, Jun Eguchi, Jun Wada

Acta medica Okayama 77 ( 3 ) 243 - 254 2023.6

Language：English Publishing type：Research paper (scientific journal)

Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BATselective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs.

DOI： 10.18926/AMO/65489

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Effects of Agalsidase Alfa Enzyme Replacement Therapy on Left Ventricular Hypertrophy on Electrocardiogram in a Female Patient with Fabry Disease. Reviewed

Kazufumi Nakamura, Hiroshi Morita, Yoichi Takaya, Yukihiro Saito, Toru Miyoshi, Hiroshi Morinaga, Hitoshi Sugiyama, Jun Wada, Hiroshi Ito

International heart journal 64 ( 3 ) 502 - 505 2023.5

Language：English Publishing type：Research paper (scientific journal)

Fabry disease is an X-linked lysosomal storage disorder caused by defective enzyme activity of α-galactosidase A and treated with enzyme replacement therapy (ERT) with recombinant α-galactosidase. ERT reduces left ventricular mass assessed by echocardiography or magnetic resonance imaging. However, electrocardiogram changes during ERT have not been fully elucidated. In the present case, ERT with agalsidase alfa for 4 years decreased QRS voltage and negative T depth along with a reduction of left ventricular mass and wall thickness and improvement of symptoms in a female patient with Fabry disease. Long-term observation of electrocardiogram changes might be useful for determining the efficacy of ERT in this case.

DOI： 10.1536/ihj.22-752

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Amelioration of nephritis in receptor for advanced glycation end-products (RAGE)-deficient lupus-prone mice through neutrophil extracellular traps. Reviewed International journal

Haruki Watanabe, Masataka Kubo, Akihiko Taniguchi, Yosuke Asano, Sumie Hiramatsu-Asano, Keiji Ohashi, Sonia Zeggar, Eri Katsuyama, Takayuki Katsuyama, Katsue Sunahori-Watanabe, Ken-Ei Sada, Yoshinori Matsumoto, Yasuhiko Yamamoto, Hiroshi Yamamoto, Myoungsun Son, Jun Wada

Clinical immunology (Orlando, Fla.) 250 109317 - 109317 2023.5

Language：English Publishing type：Research paper (scientific journal)

The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor that regulates inflammation, cell migration, and cell fate. Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease. To understand the function of RAGE in SLE, we generated RAGE-deficient (Ager-/-) lupus-prone mice by backcrossing MRL/MpJ-Faslpr/J (MRL-lpr) mice with Ager-/- C57BL/6 mice. In 18-week-old Ager-/- MRL-lpr, the weights of the spleen and lymph nodes, as well as the frequency of CD3+CD4-CD8- cells, were significantly decreased. Ager-/- MRL-lpr mice had significantly reduced urine albumin/creatinine ratios and markedly improved renal pathological scores. Moreover, neutrophil infiltration and neutrophil extracellular trap formation in the glomerulus were significantly reduced in Ager-/- MRL-lpr. Our study is the first to reveal that RAGE can have a pathologic role in immune cells, particularly neutrophils and T cells, in inflammatory tissues and suggests that the inhibition of RAGE may be a potential therapeutic strategy for SLE.

DOI： 10.1016/j.clim.2023.109317

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Association of alcohol consumption and fatigue in SLE: A cross-sectional study from Lupus Registry of Nationwide Institution (LUNA) cohort. Reviewed International journal

Yu Katayama, Yoshia Miyawaki, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Keiji Ohashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Nobuyuki Yajima, Yasuhiro Shimojima, Ryusuke Yoshimi, Kunihiro Ichinose, Hiroshi Kajiyama, Michio Fujiwara, Shuzo Sato, Jun Wada

Lupus 32 ( 4 ) 531 - 537 2023.4

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Fatigue is one of the most common complaints and is a potentially modifiable issue in systemic lupus erythematosus (SLE). Studies suggest that alcohol consumption has a protective effect against the development of SLE; however, an association between alcohol consumption and fatigue in patients with SLE has not been studied. Here, we assessed whether alcohol consumption was associated with fatigue using lupus patient-reported outcomes (LupusPRO). METHODS: This cross-sectional study, conducted between 2018 and 2019, included 534 patients (median age, 45 years; 87.3% female) from 10 institutions in Japan. The main exposure was alcohol consumption, which was defined as the frequency of drinking [<1 day/month (none group), ≤1 day/week (moderate group), and ≥2 days/week (frequent group)]. The outcome measure was the Pain Vitality domain score in LupusPRO. Multiple regression analysis was performed as the primary analysis after adjusting for confounding factors, such as age, sex, and damage. Subsequently, the same analysis was performed as a sensitivity analysis after multiple imputations (MIs) for missing data (n = 580). RESULTS: In total, 326 (61.0%) patients were categorized into the none group, 121 (22.7%) into the moderate group, and 87 (16.3%) into the frequent group. The frequent group was independently associated with less fatigue compared with none group [β = 5.98 (95% CI 0.19-11.76), p = 0.04], and the results did not substantially deviate after MI. CONCLUSIONS: Frequent drinking was associated with less fatigue, which highlights the need for further longitudinal studies focusing on drinking habits in patients with SLE.

DOI： 10.1177/09612033231159471

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The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study. Reviewed International journal

Yasuhiro Onishi, Haruhito A Uchida, Yohei Maeshima, Yuka Okuyama, Nozomu Otaka, Haruyo Ujike, Keiko Tanaka, Hidemi Takeuchi, Kenji Tsuji, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Shinji Kitamura, Hitoshi Sugiyama, Kosuke Ota, Keisuke Maruyama, Makoto Hiramatsu, Yoshiyuki Oshiro, Shigeru Morioka, Keiichi Takiue, Kazuyoshi Omori, Masaki Fukushima, Naoyuki Gamou, Hiroshi Hirata, Ryosuke Sato, Hirofumi Makino, Jun Wada

Journal of personalized medicine 13 ( 4 ) 2023.3

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. METHODS: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. RESULTS: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 ± 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). CONCLUSION: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.

DOI： 10.3390/jpm13040582

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Serum sCD40L and IL-31 in Association with Early Phase of IgA Nephropathy. Reviewed International journal

Keiko Tanaka, Hitoshi Sugiyama, Hiroshi Morinaga, Masashi Kitagawa, Yuzuki Kano, Yasuhiro Onishi, Koki Mise, Katsuyuki Tanabe, Haruhito A Uchida, Jun Wada

Journal of clinical medicine 12 ( 5 ) 2023.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. RESULTS: Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. CONCLUSIONS: The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.

DOI： 10.3390/jcm12052023

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Association between Urinary Creatinine Excretion and Hypothyroidism in Patients with Chronic Kidney Disease. Reviewed International journal

Natsumi Matsuoka-Uchiyama, Kenji Tsuji, Kensaku Takahashi, Kazuhiko Fukushima, Hidemi Takeuchi, Shinji Kitamura, Kenichi Inagaki, Haruhito A Uchida, Jun Wada

Diagnostics (Basel, Switzerland) 13 ( 4 ) 2023.2

Language：English Publishing type：Research paper (scientific journal)

While hypothyroidism increases serum creatinine (Cr) levels, it is uncertain whether the elevation is mediated via a decline in the glomerular filtration rate (GFR) or the reflection of enhanced Cr production from the muscles or both. In the present study, we explored an association between urinary Cr excretion rate (CER) and hypothyroidism. A total of 553 patients with chronic kidney disease were enrolled in a cross-sectional study. Multiple linear regression analysis was performed to explore the association between hypothyroidism and urinary CER. The mean urinary CER was 1.01 ± 0.38 g/day and 121 patients (22%) had hypothyroidism. The multiple linear regression analysis revealed explanatory variables with urinary CER, including age, sex, body mass index, 24 h Cr clearance (24hrCcr), and albumin while hypothyroidism was not considered an independent explanatory variable. In addition, scatter plot analysis with regression fit line representing the association between estimated GFR calculated using s-Cr (eGFRcre) and 24hrCcr revealed that eGFRcre and 24hrCcr had strong correlations with each other in hypothyroid patients as well as euthyroid patients. Collectively, hypothyroidism was not considered an independent explanatory variable for urinary CER in the present study and eGFRcre is a useful marker to evaluate kidney function regardless of the presence of hypothyroidism.

DOI： 10.3390/diagnostics13040669

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Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice. Reviewed

Kaori Oda, Satoshi Miyamoto, Ryo Kodera, Jun Wada, Kenichi Shikata

Journal of diabetes investigation 14 ( 2 ) 205 - 220 2023.2

Language：English Publishing type：Research paper (scientific journal)

AIMS/INTRODUCTION: Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-Ay /TaJcl (KK-Ay) mice against DKD progression. MATERIALS AND METHODS: Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. RESULTS: Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. CONCLUSIONS: These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.

DOI： 10.1111/jdi.13930

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Genome-wide association study of the risk of chronic kidney disease and kidney-related traits in the Japanese population: J-Kidney-Biobank. Reviewed International journal

Yuka Sugawara, Yosuke Hirakawa, Hajime Nagasu, Akira Narita, Akihiro Katayama, Jun Wada, Miho Shimizu, Takashi Wada, Hiromasa Kitamura, Toshiaki Nakano, Hideki Yokoi, Motoko Yanagita, Shin Goto, Ichiei Narita, Seizo Koshiba, Gen Tamiya, Masaomi Nangaku, Masayuki Yamamoto, Naoki Kashihara

Journal of human genetics 68 ( 2 ) 55 - 64 2023.2

Language：English Publishing type：Research paper (scientific journal)

Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m2 or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.

DOI： 10.1038/s10038-022-01094-1

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Metformin and Its Immune-Mediated Effects in Various Diseases. Reviewed International journal

Ichiro Nojima, Jun Wada

International journal of molecular sciences 24 ( 1 ) 2023.1

Language：English Publishing type：Research paper (scientific journal)

Metformin has been a long-standing prescribed drug for treatment of type 2 diabetes (T2D) and its beneficial effects on virus infection, autoimmune diseases, aging and cancers are also recognized. Metformin modulates the differentiation and activation of various immune-mediated cells such as CD4+ and CD+8 T cells. The activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) pathway may be involved in this process. Recent studies using Extracellular Flux Analyzer demonstrated that metformin alters the activities of glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and glutaminolysis, which tightly link to the modulation of cytokine production in CD4+ and CD+8 T cells in various disease states, such as virus infection, autoimmune diseases, aging and cancers.

DOI： 10.3390/ijms24010755

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Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia. Reviewed International journal

Akinori Hara, Takashi Wada, Eri Muso, Shoichi Maruyama, Sawako Kato, Kengo Furuichi, Kenichi Yoshimura, Tadashi Toyama, Norihiko Sakai, Hiroyuki Suzuki, Tatsuo Tsukamoto, Mariko Miyazaki, Eiichi Sato, Masanori Abe, Yugo Shibagaki, Ichiei Narita, Shin Goto, Yuichi Sakamaki, Hitoshi Yokoyama, Noriko Mori, Satoshi Tanaka, Yukio Yuzawa, Midori Hasegawa, Takeshi Matsubara, Jun Wada, Katsuyuki Tanabe, Kosuke Masutani, Yasuhiro Abe, Kazuhiko Tsuruya, Shouichi Fujimoto, Shuji Iwatsubo, Akihiro Tsuda, Hitoshi Suzuki, Kenji Kasuno, Yoshio Terada, Takeshi Nakata, Noriaki Iino, Tadashi Sofue, Hitomi Miyata, Toshiaki Nakano, Takayasu Ohtake, Shuzo Kobayashi

Blood purification 52 ( 4 ) 373 - 381 2023

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

DOI： 10.1159/000527900

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E3-ubiquitin ligases and recent progress in osteoimmunology. Reviewed International journal

Yosuke Asano, Yoshinori Matsumoto, Jun Wada, Robert Rottapel

Frontiers in immunology 14 1120710 - 1120710 2023

Language：English Publishing type：Research paper (scientific journal)

Ubiquitin-mediated proteasomal degradation is a post-transcriptional protein modification that is comprised of various components including the 76-amino acid protein ubiquitin (Ub), Ub-activating enzyme (E1), Ub-conjugating enzyme (E2), ubiquitin ligase (E3), deubiquitinating enzyme (DUB) and proteasome. We and others have recently provided genetic evidence showing that E3-ubiquitin ligases are associated with bone metabolism, the immune system and inflammation through ubiquitylation and subsequent degradation of their substrates. Dysregulation of the E3-ubiquitin ligase RNF146-mediated degradation of the adaptor protein 3BP2 (SH3 domain-binding protein 2) causes cherubism, an autosomal dominant disorder associated with severe inflammatory craniofacial dysmorphia syndrome in children. In this review, on the basis of our discoveries in cherubism, we summarize new insights into the roles of E3-ubiquitin ligases in the development of human disorders caused by an abnormal osteoimmune system by highlighting recent genetic evidence obtained in both human and animal model studies.

DOI： 10.3389/fimmu.2023.1120710

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Editorial: Myriad types of cell death in nephropathy and their veiled potential. Reviewed International journal

Jun Wada, Rashmi S Tupe, Isha Sharma

Frontiers in endocrinology 14 1251148 - 1251148 2023

A case of sitosterolaemia-caused systemic large-vessel stenosis mimicking Takayasu arteritis in which FDG-PET provided a clue for the differential diagnosis. Reviewed International journal

Takato Nakadoi, Eri Katsuyama, Kazuya Matsumoto, Kenta Shidahara, Kei Hirose, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Hayato Tada, Jun Wada

Rheumatology advances in practice 7 ( 3 ) rkad096 2023

Cover Image, Volume 24, Issue 12

Takashi Kadowaki, Hiroshi Maegawa, Hirotaka Watada, Daisuke Yabe, Koichi Node, Toyoaki Murohara, Jun Wada

Diabetes, Obesity and Metabolism 2022.12

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study Reviewed

Haruhito A. Uchida, Hirofumi Nakajima, Masami Hashimoto, Akihiko Nakamura, Tomokazu Nunoue, Kazuharu Murakami, Takeshi Hosoya, Kiichi Komoto, Takashi Taguchi, Takaaki Akasaka, Kazuhito Shiosakai, Kotaro Sugimoto, Jun Wada

ADVANCES IN THERAPY 39 ( 11 ) 5158 - 5175 2022.11

A case of recurrent IgG4-related disease successfully treated with belimumab after remission of systemic lupus erythematosus Reviewed

Yu Katayama, Takayuki Katsuyama, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

RHEUMATOLOGY 61 ( 10 ) E308 - E310 2022.10

Effects of Wnt-beta-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells Reviewed

Eisaku Morimoto, Kenichi Inagaki, Motoshi Komatsubara, Tomohiro Terasaka, Yoshihiko Itoh, Satoshi Fujisawa, Erika Sasaki, Yuki Nishiyama, Takayuki Hara, Jun Wada

JOURNAL OF THE ENDOCRINE SOCIETY 6 ( 10 ) 2022.10

Simulation for ultrasound-guided renal biopsy using boiled egg Reviewed

Kenji Tsuji, Shinji Kitamura, Haruhito A. Uchida, Jun Wada

NEPHROLOGY 27 ( 9 ) 753 - 757 2022.9

The association between hypothyroidism and proteinuria in patients with chronic kidney disease: a cross-sectional study Reviewed

Natsumi Matsuoka-Uchiyama, Kenji Tsuji, Yizhen Sang, Kensaku Takahashi, Kazuhiko Fukushima, Hidemi Takeuchi, Kenichi Inagaki, Haruhito A. Uchida, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada

SCIENTIFIC REPORTS 12 ( 1 ) 2022.9

Cilostazol Attenuates AngII-Induced Cardiac Fibrosis in apoE Deficient Mice Reviewed

Yoshiko Hada, Haruhito A. Uchida, Ryoko Umebayashi, Masashi Yoshida, Jun Wada

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 ( 16 ) 2022.8

Interconnection between cardiovascular, renal and metabolic disorders: A narrative review with a focus on Japan Reviewed

Takashi Kadowaki, Hiroshi Maegawa, Hirotaka Watada, Daisuke Yabe, Koichi Node, Toyoaki Murohara, Jun Wada

DIABETES OBESITY & METABOLISM 2022.8

Edaravone Attenuated Angiotensin II-Induced Atherosclerosis and Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice Reviewed

Haruhito A. Uchida, Tetsuharu Takatsuka, Yoshiko Hada, Ryoko Umebayashi, Hidemi Takeuchi, Kenichi Shikata, Venkateswaran Subramanian, Alan Daugherty, Jun Wada

BIOMOLECULES 12 ( 8 ) 2022.8

Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus. Reviewed

Sumie Hiramatsu-Asano, Jun Wada

Acta medica Okayama 76 ( 4 ) 359 - 371 2022.8

Language：English Publishing type：Research paper (scientific journal)

Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE.

DOI： 10.18926/AMO/63887

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Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study Reviewed

Yuka Sugawara, Yosuke Hirakawa, Koki Mise, Kosuke Kashiwabara, Ko Hanai, Satoshi Yamaguchi, Akihiro Katayama, Yasuhiro Onishi, Yui Yoshida, Naoki Kashihara, Yutaka Matsuyama, Tetsuya Babazono, Masaomi Nangaku, Jun Wada

BIOMARKERS IN MEDICINE 16 ( 10 ) 759 - 770 2022.7

Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle. Reviewed

Masafumi Tenta, Jun Eguchi, Jun Wada

Acta medica Okayama 76 ( 3 ) 235 - 245 2022.6

Language：English Publishing type：Research paper (scientific journal)

The combination of sarcopenia and obesity (sarcopenic obesity) is associated with the development of metabolic syndrome and cardiovascular events. The molecular pathways that develop sarcopenic obesity have studied intensively. Transmembrane protein 97 (TMEM97) is 176 amino acids conserved integral membrane protein with four transmembrane domains that is expressed in several types of cancer. Its physiological significance in adipose tissue and skeletal muscle has been unclear. We studied TMEM97-transgenic mice and mice lacking TMEM97, and our findings indicate that TMEM97 expression is regulated in adipose tissue and skeletal muscle from obesity. TMEM97 represses adipogenesis and promotes myogenesis in vitro. Fat-specific TMEM97 transgenic mice showed systemic insulin resistance. Mice overexpressing TMEM97 in skeletal muscle exhibited systemic insulin resistance. Mice lacking TMEM97 were protected against diet-induced obesity and insulin resistance. These phenotypes are associated with the effects of TMEM97 on inflammation genes in adipose tissue and skeletal muscle. Our findings indicates that there is a link between TMEM97 and chronic inflammation in obesity.

DOI： 10.18926/AMO/63717

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Potential Strategies for Kidney Regeneration With Stem Cells: An Overview Reviewed

Kenji Tsuji, Shinji Kitamura, Jun Wada

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 10 2022.5

Vasohibin-1 has α-tubulin detyrosinating activity in glomerular podocytes. Reviewed International journal

Tomoyo Mifune, Katsuyuki Tanabe, Yuri Nakashima, Satoshi Tanimura, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

Biochemical and biophysical research communications 599 93 - 99 2022.4

Language：English Publishing type：Research paper (scientific journal)

Podocytes are highly specialized epithelial cells in glomeruli, with a complex morphology composed of a cell body, primary processes, and foot processes, which maintain barrier function in glomerular filtration. The microtubule-based cytoskeleton is necessary for podocyte morphology. Microtubule structure and function can be affected by post-translational modification of tubulin, including detyrosination. Recent studies have shown that vasohibin-1 (VASH1), an antiangiogenic factor, has tubulin carboxypeptidase activity that causes detyrosination of α-tubulin. We aimed to examine the role of VASH1 in regulating α-tubulin detyrosination in podocytes and the potential involvement of VASH1 deficiency in renal morphology. In normal mouse kidneys, detyrosinated α-tubulin was mainly identified in glomeruli, especially in podocytes; meanwhile, in cultured immortalized podocytes, α-tubulin detyrosination was promoted with cell differentiation. Notably, α-tubulin detyrosination in glomeruli was diminished in Vash1 homozygous knockout (Vash1-/-) mice, and knockdown of VASH1 in cultured podocytes prevented α-tubulin detyrosination. Although VASH1 deficiency-induced downregulation of detyrosination caused no remarkable glomerular lesions, urinary albuminuria excretion and glomerular volume were significantly higher in Vash1-/- mice than in wild-type mice. Furthermore, decreased glomerular nephrin expression and narrower slit diaphragms width were observed in Vash1-/- mice. Taken together, we demonstrated that α-tubulin detyrosination in podocytes was mainly regulated by VASH1 and that VASH1 deficiency-mediated decreases in α-tubulin detyrosination led to minor alterations in podocyte morphology and predisposition to albuminuria. VASH1 expression and α-tubulin detyrosination may be novel targets for maintaining glomerular filtration barrier integrity.

DOI： 10.1016/j.bbrc.2022.02.047

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Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells Reviewed

Masayoshi Suda, Ippei Shimizu, Goro Katsuumi, Chieh Lun Hsiao, Yohko Yoshida, Naomi Matsumoto, Yutaka Yoshida, Akihiro Katayama, Jun Wada, Masahide Seki, Yutaka Suzuki, Shujiro Okuda, Kazuyuki Ozaki, Mayumi Nakanishi-Matsui, Tohru Minamino

SCIENTIFIC REPORTS 12 ( 1 ) 2022.4

Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation Reviewed

Kenta Ikeda, Shin Morizane, Takahiko Akagi, Sumie Hiramatsu-Asano, Kota Tachibana, Ayano Yahagi, Masanori Iseki, Hideaki Kaneto, Jun Wada, Katsuhiko Ishihara, Yoshitaka Morita, Tomoyuki Mukai

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 ( 8 ) 2022.4

Tankyrase represses autoinflammation through the attenuation of TLR2 signaling Reviewed

Yoshinori Matsumoto, Ioannis D. Dimitriou, Jose La Rose, Melissa Lim, Susan Camilleri, Napoleon Law, Hibret A. Adissu, Jiefei Tong, Michael F. Moran, Andrzej Chruscinski, Fang He, Yosuke Asano, Takayuki Katsuyama, Ken-Ei Sada, Jun Wada, Robert Rottapel

JOURNAL OF CLINICAL INVESTIGATION 132 ( 7 ) 2022.4

Kidney cyst infection through a fistula between bladder and retroperitoneal abscess in a polycystic kidney disease patient Reviewed

Takato Nakadoi, Kenji Tsuji, Takehiro Iwata, Eriko Eto, Hisashi Masuyama, Koji Tomita, Takao Hiraki, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada

NEPHROLOGY 27 ( 4 ) 383 - 384 2022.4

Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study Reviewed

Naoko Kurooka, Jun Eguchi, Kazutoshi Murakami, Shinji Kamei, Toru Kikutsuji, Sakiko Sasaki, Akiho Seki, Satoshi Yamaguchi, Ichiro Nojima, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Haruhito A. Uchida, Atsuko Nakatsuka, Kenichi Shikata, Jun Wada

JOURNAL OF CLINICAL LIPIDOLOGY 16 ( 2 ) 237 - 245 2022.3

Silica-associated systemic lupus erythematosus with lupus nephritis and lupus pneumonitis A case report and a systematic review of the literature Reviewed

Kazuhiko Fukushima, Haruhito A. Uchida, Yasuko Fuchimoto, Tomoyo Mifune, Mayu Watanabe, Kenji Tsuji, Katsuyuki Tanabe, Masaru Kinomura, Shinji Kitamura, Yosuke Miyamoto, Sae Wada, Taisaku Koyanagi, Hitoshi Sugiyama, Takumi Kishimoto, Jun Wada

MEDICINE 101 ( 7 ) 2022.2

Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray Reviewed

Yasuhiro Onishi, Koki Mise, Chieko Kawakita, Haruhito A. Uchida, Hitoshi Sugiyama, Ryosuke Sugawara, Satoshi Yamaguchi, Michihiro Yoshida, Toshiharu Mitsuhashi, Masao Yamada, Jun Hirabayashi, Jun Wada

AMERICAN JOURNAL OF NEPHROLOGY 53 ( 1 ) 10 - 20 2022.2

Prevalence of Chronic Kidney Disease and Variation of Its Risk Factors by the Regions in Okayama Prefecture Reviewed

Ryoko Umebayashi, Haruhito Adam Uchida, Natsumi Matsuoka-Uchiyama, Hitoshi Sugiyama, Jun Wada

JOURNAL OF PERSONALIZED MEDICINE 12 ( 1 ) 2022.1

The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study Reviewed

Natsumi Matsuoka-Uchiyama, Haruhito A. Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenichi Shikata, Jun Wada

JOURNAL OF DIABETES RESEARCH 2022 2022.1

Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4 Reviewed

Satoshi Yamaguchi, Dongxiao Zhang, Akihiro Katayama, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Jun Wada

FRONTIERS IN ENDOCRINOLOGY 12 2022.1

Real-world data on vitamin D supplementation and its impacts in systemic lupus erythematosus: Cross-sectional analysis of a lupus registry of nationwide institutions (LUNA). Reviewed International journal

Keigo Hayashi, Ken-Ei Sada, Yosuke Asano, Yu Katayama, Keiji Ohashi, Michiko Morishita, Yoshia Miyawaki, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Nobuyuki Yajima, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Jun Wada

PloS one 17 ( 6 ) e0270569 2022

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE. METHODS: A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control. RESULTS: Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups. CONCLUSIONS: Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.

DOI： 10.1371/journal.pone.0270569

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Mesenchymal stem cells-derived extracellular vesicles as 'natural' drug delivery system for tissue regeneration Reviewed

Kenji Tsuji, Shinji Kitamura, Jun Wada

BIOCELL 46 ( 4 ) 899 - 902 2022

Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism. Reviewed International journal

Natsumi Uchiyama-Matsuoka, Kenji Tsuji, Haruhito A Uchida, Shinji Kitamura, Yoshihiko Itoh, Yuki Nishiyama, Eisaku Morimoto, Satoshi Fujisawa, Tomohiro Terasaka, Takayuki Hara, Kanako Ogura-Ochi, Kenichi Inagaki, Jun Wada

Frontiers in endocrinology 13 1048863 - 1048863 2022

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism. METHODS: Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. RESULTS: Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 m2) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m2). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. CONCLUSIONS: We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.

DOI： 10.3389/fendo.2022.1048863

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THE MINIMALLY IMPORTANT DIFFERENCE AS THE INTERPRETABILITY OF EMOTIONAL HEALTH DOMAIN IN JAPANESE VERSION OF LUPUSPRO FOR SLE PATIENTS; PRELIMINARY RESULTS OF A PROSPECTIVE COHORT STUDY

Jun Wada

Annals of the Rheumatic Diseases 2022

First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency

Jun Wada

Heliyon 2022

The Beneficial Effect of Personalized Lifestyle Intervention in Chronic Kidney Disease Follow-Up Project for National Health Insurance Specific Health Checkup: A Five-Year Community-Based Cohort Study

Jun Wada

Medicina 2022

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice Reviewed

Jun Wada

Nature Aging 1 ( 12 ) 1117 - 1126 2021.12

Commentary on Intraglumerular dysfunction predicts kidney failure in the type 2 diabetes Reviewed

Jun Wada

JOURNAL OF DIABETES INVESTIGATION 12 ( 12 ) 2124 - 2125 2021.12

Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling Reviewed

Yizhen Sang, Kenji Tsuji, Kazuhiko Fukushima, Kensaku Takahashi, Shinji Kitamura, Jun Wada

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 321 ( 6 ) F740 - F756 2021.12

Presence of decoy cells for 6 months on urine cytology efficiently predicts BK virus nephropathy in renal transplant recipients Reviewed

Takanori Sekito, Motoo Araki, Kasumi Yoshinaga, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Tanabe, Hidemi Takeuchi, Hiroshi Morinaga, Masashi Kitagawa, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Hiroyuki Yanai, Yasutomo Nasu

INTERNATIONAL JOURNAL OF UROLOGY 28 ( 12 ) 1240 - 1246 2021.12

Management of corticosteroid-dependent eosinophilic interstitial nephritis A case report Reviewed

Katsuyuki Tanabe, Natsumi Matsuoka-Uchiyama, Tomoyo Mifune, Chieko Kawakita, Hitoshi Sugiyama, Jun Wada

MEDICINE 100 ( 50 ) 2021.12

Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database Reviewed

Hajime Nagasu, Yuichiro Yano, Hiroshi Kanegae, Hiddo J. L. Heerspink, Masaomi Nangaku, Yosuke Hirakawa, Yuka Sugawara, Naoki Nakagawa, Yuji Tani, Jun Wada, Hitoshi Sugiyama, Kazuhiko Tsuruya, Toshiaki Nakano, Shoichi Maruyama, Takashi Wada, Kunihiro Yamagata, Ichiei Narita, Kouichi Tamura, Motoko Yanagita, Yoshio Terada, Takashi Shigematsu, Tadashi Sofue, Takafumi Ito, Hirokazu Okada, Naoki Nakashima, Hiromi Kataoka, Kazuhiko Ohe, Mihoko Okada, Seiji Itano, Akira Nishiyama, Eiichiro Kanda, Kohjiro Ueki, Naoki Kashihara

DIABETES CARE 44 ( 11 ) 2542 - 2551 2021.11

Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control (vol 12, 727915, 2021) Reviewed

Dongxiao Zhang, Satoshi Yamaguchi, Xinhao Zhang, Boxuan Yang, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Takeshi Y. Hiyama, Atsunori Kamiya, Jun Wada

FRONTIERS IN ENDOCRINOLOGY 12 2021.11

Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms Reviewed

Shogo Watari, Motoo Araki, Jun Matsumoto, Kasumi Yoshinaga, Takanori Sekito, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Koichiro Wada, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Noritaka Ariyoshi, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

DRUG METABOLISM AND PHARMACOKINETICS 40 2021.10

Sodium-Glucose Cotransporter 2 Inhibitors Work as a "Regulator" of Autophagic Activity in Overnutrition Diseases Reviewed

Kazuhiko Fukushima, Shinji Kitamura, Kenji Tsuji, Jun Wada

FRONTIERS IN PHARMACOLOGY 12 2021.10

Feasible kidney donation with living marginal donors, including diabetes mellitus Reviewed

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Takanori Sekito, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Katsuyuki Tanabe, Hidemi Takeuchi, Masashi Kitagawa, Shinji Kitamura, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

IMMUNITY INFLAMMATION AND DISEASE 9 ( 3 ) 1061 - 1068 2021.9

Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases Reviewed

Noriko Fujiwara, Mayu Watanabe, Akihiro Katayama, Yohei Noda, Jun Eguchi, Hitomi Kataoka, Shunsuke Kagawa, Jun Wada

CLINICAL CASE REPORTS 9 ( 9 ) 2021.9

Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 (vol 11, 5991, 2021) Reviewed

Tomokazu Nunoue, Satoshi Yamaguchi, Sanae Teshigawara, Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Toshiro Niki, Jun Wada

SCIENTIFIC REPORTS 11 ( 1 ) 2021.9

Total vascular resistance, augmentation index, and augmentation pressure increase in patients with peripheral artery disease. Reviewed International journal

Rika Takemoto, Haruhito A Uchida, Hironobu Toda, Ken Okada, Fumio Otsuka, Hiroshi Ito, Jun Wada

Medicine 100 ( 32 ) e26931 2021.8

Language：English Publishing type：Research paper (scientific journal)

ABSTRACT: Peripheral arterial disease (PAD) is one of major vascular diseases which frequently coexists with coronary arterial disease and cerebrovascular disease. The patients with PAD have a poor prognosis when it progresses. A new blood pressure testing device enables to simultaneously measure brachial blood pressure (BP), central BP, and several vascular parameters, with easy and non-invasive, in a short time. Here, we aimed to evaluate these arterial stiffness parameters in patients with PAD.In this study, 243 consecutive patients who were suspected of having PAD and referred to our hospital from September 2016 to June 2019, were registered. Several parameters, such as brachial BP, central BP, aortic pulse wave velocity (aPWV), total vascular resistance (TVR), augmentation index (AI) and augmentation pressure (AP), were determined by Mobil-O-Graph. Ankle-brachial pressure index (ABI) was used to define PAD (ABI ≤ 0.9 as PAD). The relationship between PAD and central BP, aPWV, TVR, AI, or AP were investigated.One hundred sixty-two patients (67%) were categorized as the PAD group and 81 patients (33%) as the non-PAD group. In the PAD group, the systolic brachial BP and central systolic BP were significantly higher than those in the non-PAD group (138 ± 24 mmHg vs 131 ± 19 mmHg, P < .05, 125 ± 22 mmHg vs 119 ± 18 mmHg, P < .05, respectively). TVR, AI, and AP were significantly higher in the PAD group (1785 ± 379 dyn s/cm5 vs 1661 ± 317 dyn s/cm5, P < .05, 26.2 ± 13.0% vs 22.2 ± 13.3%, P < .05, 13.5 ± 9.4 mmHg vs 10.7 ± 7.2 mmHg, P < .05, respectively). No significant differences in diastolic BP, central diastolic BP, and aPWV were found between the groups. Multivariate logistic regression analysis revealed that PAD was significantly associated with TVR, AI, and AP (P < .05, respectively).TVR/AP/AI were significantly higher in the PAD group than in the non-PAD group.

DOI： 10.1097/MD.0000000000026931

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GENOME-WIDE ASSOCIATION STUDY FOR THE ONSET OF CHRONIC KIDNEY DISEASE IN JAPANESE POPULATION Reviewed

Yuka Sugawara, Yosuke Hirakawa, Hajime Nagasu, Akira Narita, Jun Wada, Takashi Wada, Toshiaki Nakano, Motoko Yanagita, Ichiei Narita, Seizo Koshiba, Gen Tamiya, Masaomi Nangaku, Masayuki Yamamoto, Naoki Kashihara

NEPHROLOGY 26 7 - 8 2021.8

Successful deceased donor kidney transplantation to a recipient with a history of COVID-19 treatment Reviewed

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Kou Hasegawa, Takanori Sekito, Shuji Miyake, Shogo Watari, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Katsuyuki Tanabe, Hidemi Takeuchi, Yuri Nakashima, Masaru Kinomura, Herik Acosta, Yosuke Mitsui, Risa Kubota, Hirochika Nakajima, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Fumio Otsuka, Jun Wada, Yasutomo Nasu

JOURNAL OF INFECTION AND CHEMOTHERAPY 27 ( 7 ) 1097 - 1101 2021.7

RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion (vol 11, 665273, 2021) Reviewed

Fang He, Yoshinori Matsumoto, Yosuke Asano, Yuriko Yamamura, Takayuki Katsuyama, Jose La Rose, Nahoko Tomonobu, Ni Luh Gede Yoni Komalasari, Masakiyo Sakaguchi, Robert Rottapel, Jun Wada

FRONTIERS IN ONCOLOGY 11 2021.7

Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study Reviewed

Mariko Tsuchida-Nishiwaki, Haruhito A. Uchida, Hidemi Takeuchi, Noriyuki Nishiwaki, Yohei Maeshima, Chie Saito, Hitoshi Sugiyama, Jun Wada, Ichiei Narita, Tsuyoshi Watanabe, Seiichi Matsuo, Hirofumi Makino, Akira Hishida, Kunihiro Yamagata

SCIENTIFIC REPORTS 11 ( 1 ) 2021.7

The effect of Humanitude care methodology on improving empathy: a six-year longitudinal study of medical students in Japan Reviewed

Yusuke Fukuyasu, Hitomi U. Kataoka, Miwako Honda, Toshihide Iwase, Hiroko Ogawa, Masaru Sato, Mayu Watanabe, Chikako Fujii, Jun Wada, Jennifer DeSantis, Mohammadreza Hojat, Joseph S. Gonnella

BMC MEDICAL EDUCATION 21 ( 1 ) 2021.6

ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study Reviewed

Shogo Watari, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

TRANSPLANTATION PROCEEDINGS 53 ( 5 ) 1494 - 1500 2021.6

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2) Reviewed

Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Satoshi Miyamoto, Haruhito A. Uchida, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhiro Miyashita, Shinichiro Ando, Tomokazu Nunoue, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

FRONTIERS IN CARDIOVASCULAR MEDICINE 8 2021.5

Vasohibin-2 Aggravates Development of Ascending Aortic Aneurysms but not Abdominal Aortic Aneurysms nor Atherosclerosis in ApoE-Deficient Mice Reviewed

Nozomu Otaka, Haruhito A. Uchida, Michihiro Okuyama, Yoshiko Hada, Yasuhiro Onishi, Yuki Kakio, Hidemi Takeuchi, Ryoko Umebayashi, Katsuyuki Tanabe, Venkateswaran Subramanian, Alan Daugherty, Yasufumi Sato, Jun Wada

AMERICAN JOURNAL OF HYPERTENSION 34 ( 5 ) 467 - 475 2021.5

Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells Reviewed

Satoshi Fujisawa, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Takahiro Nada, Jun Wada, Fumio Otsuka

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 ( 9 ) 2021.5

Endonuclease increases efficiency of osteoblast isolation from murine calvariae. Reviewed International journal

Yosuke Asano, Yoshinori Matsumoto, Jose La Rose, Fang He, Takayuki Katsuyama, Wang Ziyi, Shigetomo Tsuji, Hiroshi Kamioka, Robert Rottapel, Jun Wada

Scientific reports 11 ( 1 ) 8502 - 8502 2021.4

THE IMPACT OF BLOOD PRESSURE MANAGEMENT IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A MULTICENTER PROSPECTIVE COHORT STUDY IN JAPAN Reviewed

Mariko Nishiwaki, Haruhito A. Uchida, Nozomu Otaka, Yoshiko Hada, Yasuhiro Onishi, Natsumi Uchiyama, Shugo Okamoto, Rika Takemoto, Masashi Kitagawa, Hitoshi Sugiyama, Chie Saito, Kunihiro Yamagata, Jun Wada

JOURNAL OF HYPERTENSION 39 E122 - E123 2021.4

Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Macrophage Reviewed

Yoshiko Hada, Haruhito A. Uchida, Jun Wada

BIOMED RESEARCH INTERNATIONAL 2021 2021.4

Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study. Reviewed International journal

Yoshia Miyawaki, Sayaka Shimizu, Yusuke Ogawa, Ken-Ei Sada, Yu Katayama, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu-Asano, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nobuyuki Yajima, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Hajime Yamazaki, Yosuke Yamamoto, Jun Wada, Shunichi Fukuhara

Arthritis research & therapy 23 ( 1 ) 79 - 79 2021.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS). METHODS: This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of ≥ 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use. RESULTS: Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (β coefficient = - 2.54 [95% confidence interval - 4.48 to - 0.60], P = 0.01). CONCLUSIONS: Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health.

DOI： 10.1186/s13075-021-02466-2

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A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease Reviewed

Atsuko Nakatsuka, Satoshi Yamaguchi, Jun Eguchi, Shigeru Kakuta, Yoichiro Iwakura, Hitoshi Sugiyama, Jun Wada

COMMUNICATIONS BIOLOGY 4 ( 1 ) 2021.3

Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy Reviewed

Chieko Kawakita, Koki Mise, Yasuhiro Onishi, Hitoshi Sugiyama, Michihiro Yoshida, Masao Yamada, Jun Wada

SCIENTIFIC REPORTS 11 ( 1 ) 2021.2

Granulomatosis with polyangiitis with obstructive pneumonia progressing to hypertrophic pachymeningitis: A case report. Reviewed International journal

Keigo Hayashi, Haruki Watanabe, Yuriko Yamamura, Yosuke Asano, Yu Katayama, Sumie Hiramatsu-Asano, Keiji Ohashi, Michiko Morishita, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

Medicine 100 ( 3 ) e24028 2021.1

Language：English Publishing type：Research paper (scientific journal)

RATIONALE: Bronchial involvement alone is a rare initial manifestation of granulomatosis with polyangiitis (GPA). Herein, we report a case of refractory GPA with obstructive pneumonia caused by bronchial involvement. PATIENT CONCERNS: A 65-year-old man complained of a 2-week cough and fever. DIAGNOSES: Considering the presence of opacities and multiple consolidations in both lungs due to obstruction or stenosis on the bronchus, which did not respond to antibiotics, and proteinase-3-antineutrophil cytoplasmic autoantibody positivity, he was diagnosed with GPA. Positron emission tomography- computed tomography scan revealed no abnormal findings in the upper respiratory tract. INTERVENTIONS: He was treated with prednisolone (PSL, 50 mg/d) and intravenous cyclophosphamide. OUTCOMES: His general and respiratory symptoms improved. However, 8 weeks after PSL treatment at 20 mg/d, he developed a relapse of vasculitis along with sinusitis and hypertrophic pachymeningitis. Hence, PSL treatment was resumed to 50 mg/d, and weekly administration of rituximab was initiated. Consequently, the symptoms gradually mitigated. LESSONS: GPA with bronchial involvement is often intractable and requires careful follow-up, which should include upper respiratory tract and hypertrophic pachymeningitis assessment.

DOI： 10.1097/MD.0000000000024028

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Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia Reviewed

Takashi Wada, Akinori Hara, Eri Muso, Shoichi Maruyama, Sawako Kato, Kengo Furuichi, Kenichi Yoshimura, Tadashi Toyama, Norihiko Sakai, Hiroyuki Suzuki, Tatsuo Tsukamoto, Mariko Miyazaki, Eiichi Sato, Masanori Abe, Yugo Shibagaki, Ichiei Narita, Shin Goto, Yuichi Sakamaki, Hitoshi Yokoyama, Noriko Mori, Yukio Yuzawa, Midori Hasegawa, Takeshi Matsubara, Jun Wada, Katsuyuki Tanabe, Kosuke Masutani, Yasuhiro Abe, Kazuhiko Tsuruya, Shouichi Fujimoto, Shuji Iwatsubo, Akihiro Tsuda, Hitoshi Suzuki, Kenji Kasuno, Yoshio Terada, Takeshi Nakata, Noriaki Iino, Tadashi Sofue, Hitomi Miyata, Toshiaki Nakano, Takayasu Ohtake, Shuzo Kobayashi

CLINICAL AND EXPERIMENTAL NEPHROLOGY 25 ( 1 ) 1 - 8 2021.1

MicroRNAs as Biomarkers for Nephrotic Syndrome Reviewed

Kenji Tsuji, Shinji Kitamura, Jun Wada

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 ( 1 ) 2021.1

The resolution of immunofluorescent pathological images affects diagnosis for not only artificial intelligence but also human Reviewed

Kensaku Takahashi, Shinji Kitamura, Kazuhiko Fukushima, Yizhen Sang, Kenji Tsuji, Jun Wada

Journal of Nephropathology 10 ( 3 ) 2021

Current Status of Familial LCAT Deficiency in Japan Reviewed

Masayuki Kuroda, Hideaki Bujo, Koutaro Yokote, Takeyoshi Murano, Takashi Yamaguchi, Masatsune Ogura, Katsunori Ikewaki, Masahiro Koseki, Yasuo Takeuchi, Atsuko Nakatsuka, Mika Hori, Kota Matsuki, Takashi Miida, Shinji Yokoyama, Jun Wada, Mariko Harada-Shiba

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 28 ( 7 ) 679 - 691 2021

Acute Kidney Injury Caused by Evans Syndrome with Systemic Lupus Erythematosus and Systemic Sclerosis Reviewed

Natsumi Matsuoka, Haruki Watanabe, Naoko Kurooka, Sumari Kato, Chika Higashi, Katsuyuki Tanabe, Masaru Kinomura, Nobuharu Fujii, Ken-Ei Sada, Hitoshi Sugiyama, Jun Wada

INTERNAL MEDICINE 60 ( 7 ) 1055 - 1060 2021

Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes Reviewed

The Mon La, Hiromi Tachibana, Shun-Ai Li, Tadashi Abe, Sayaka Seiriki, Hikaru Nagaoka, Eizo Takashima, Tetsuya Takeda, Daisuke Ogawa, Shin-ichi Makino, Katsuhiko Asanuma, Masami Watanabe, Xuefei Tian, Shuta Ishibe, Ayuko Sakane, Takuya Sasaki, Jun Wada, Kohji Takei, Hiroshi Yamada

FASEB JOURNAL 34 ( 12 ) 16449 - 16463 2020.12

Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection Reviewed

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Haruhito Adam Uchida, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

INTERNATIONAL JOURNAL OF UROLOGY 27 ( 12 ) 1136 - 1142 2020.12

Takayasu phlebitis Reviewed

Yu Katayama, Yoshinori Matsumoto, Yuriko Yamamura, Yosuke Asano, Keigo Hayashi, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Narazaki, Ken-Ei Sada, Jun Wada

RHEUMATOLOGY 59 ( 12 ) E131 - E133 2020.12

Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis. Reviewed International journal

Keigo Hayashi, Ken-Ei Sada, Yosuke Asano, Sumie Hiramatsu Asano, Yuriko Yamamura, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Narazaki, Yoshinori Matsumoto, Jun Wada

Scientific reports 10 ( 1 ) 18715 - 18715 2020.10

Language：English Publishing type：Research paper (scientific journal)

Renal impairment is a major concern in patients taking high-dose methotrexate (MTX) for malignancy, but it has not been fully explored in rheumatoid arthritis (RA) patients taking low-dose MTX. This study aimed to elucidate the dose-dependent effects of MTX on the renal function of patients with RA. We retrospectively reviewed 502 consecutive RA patients who were prescribed MTX for ≥ 1 year at Okayama University Hospital between 2006 and 2018. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over 1 year. The association between MTX dosage (< 8, 8-12, and ≥ 12 mg/week) and the change in eGFR was evaluated using multiple linear regression analysis with adjustment for possible confounding factors including age, sex, disease duration, body weight, comorbidity, baseline eGFR, concomitant treatment, and disease activity. Mean patient age was 63 years; 394 (78%) were female. Median disease duration was 77 months, while mean MTX dosage was 8.6 mg/week. The last 1-year change of eGFR (mean ± SD) in patients treated with MTX < 8 (n = 186), 8-12 (n = 219), ≥ 12 mg/week (n = 97) decreased by 0.2 ± 7.3, 0.6 ± 8.6, and 4.5 ± 7.9 mL/min/1.73 m2/year, respectively (p < 0.0001). After adjustment for the confounding factors, MTX ≥ 12 mg/week was still correlated with a decrease in 1-year eGFR (beta-coefficient: - 2.5; 95% confidence interval, - 4.3 to - 0.6; p = 0.0089) in contrast to MTX 8-12 mg/week. Careful monitoring of renal function is required in patients with MTX ≥ 12 mg/week over the course of RA treatment regardless of disease duration.

DOI： 10.1038/s41598-020-75655-9

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Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice Reviewed

Yoshiko Hada, Haruhito A. Uchida, Tomoyuki Mukai, Fumiaki Kojima, Masashi Yoshida, Hidemi Takeuchi, Yuki Kakio, Nozomu Otaka, Yoshitaka Morita, Jun Wada

CLINICAL SCIENCE 134 ( 20 ) 2771 - 2787 2020.10

Multicentric Reticulohistiocytosis in a Patient with Hand Contracture. Reviewed

Tomoko Kawabata, Ken-Ei Sada, Haruki Watanabe, Jun Wada

Internal medicine (Tokyo, Japan) 59 ( 18 ) 2337 - 2338 2020.9

Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis Reviewed

Ichiro Nojima, Shingo Eikawa, Nahoko Tomonobu, Yoshiko Hada, Nobuo Kajitani, Sanae Teshigawara, Satoshi Miyamoto, Atsuhito Tone, Haruhito A. Uchida, Atsuko Nakatsuka, Jun Eguchi, Kenichi Shikata, Heiichiro Udono, Jun Wada

SCIENTIFIC REPORTS 10 ( 1 ) 2020.9

Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells Reviewed

Natsumi Matsuoka-Uchiyama, Kenji Tsuji, Kazuhiko Fukushima, Shinji Kitamura, Haruhito A. Uchida, Hitoshi Sugiyama, Naoki Takahashi, Masayuki Iwano, Jun Wada

KIDNEY INTERNATIONAL REPORTS 5 ( 9 ) 1576 - 1580 2020.9

Podocytopathy as 'stand-alone' involvement in systemic lupus erythematosus: a case report. Reviewed International journal

Kenji Tsuji, Yoko Takatsu, Yu Katayama, Kazuhiko Fukushima, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada

Lupus 29 ( 9 ) 1148 - 1150 2020.8

Tubulointerstitial Nephritis and Uveitis Caused by Sjögren Syndrome Without Dryness. Reviewed International journal

Soichiro Sugitani, Kenji Tsuji, Toshio Yamanari, Yoichi Hasegawa, Kentaro Inoue, Yuka Sogabe, Yukari Nakano, Shinji Kitamura, Tsutomu Ishizu, Jun Wada

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2020.7

Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors. Reviewed International journal

Kenji Tsuji, Shinji Kitamura, Yizhen Sang, Kazuhiko Fukushima, Jun Wada

Stem cell research 46 101865 - 101865 2020.7

Language：English Publishing type：Research paper (scientific journal)

Adult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.

DOI： 10.1016/j.scr.2020.101865

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Deep Learning Could Diagnose Diabetic Nephropathy with Renal Pathological Immunofluorescent Images Reviewed

Shinji Kitamura, Kensaku Takahashi, Yizhen Sang, Kazuhiko Fukushima, Kenji Tsuji, Jun Wada

DIAGNOSTICS 10 ( 7 ) 2020.7

The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway. Reviewed International journal

Yoshiko Hada, Haruhito A Uchida, Nozomu Otaka, Yasuhiro Onishi, Shugo Okamoto, Mariko Nishiwaki, Rika Takemoto, Hidemi Takeuchi, Jun Wada

International journal of molecular sciences 21 ( 12 ) 2020.6

Language：English Publishing type：Research paper (scientific journal)

The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-β-galactosidase (SA-β-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H2O2 for an hour, then cultured in the absence or presence of 0.5-5.0 μM CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H2O2 treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway.

DOI： 10.3390/ijms21124527

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Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury. Reviewed International journal

Yizhen Sang, Kenji Tsuji, Akiko Inoue-Torii, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

International journal of molecular sciences 21 ( 11 ) 2020.6

Language：English Publishing type：Research paper (scientific journal)

Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury.

DOI： 10.3390/ijms21114099

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Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study. Reviewed International journal

Eri Katsuyama, Yoshia Miyawaki, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu-Asano, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Jun Wada

BMC nephrology 21 ( 1 ) 208 - 208 2020.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). METHODS: In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. RESULTS: The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). CONCLUSION: As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

DOI： 10.1186/s12882-020-01868-9

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Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury Reviewed

Hiromasa Miyake, Katsuyuki Tanabe, Satoshi Tanimura, Yuri Nakashima, Tomoyo Morioka, Kana Masuda, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 ( 12 ) 2020.6

The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway Reviewed

Yoshiko Hada, Haruhito A. Uchida, Nozomu Otaka, Yasuhiro Onishi, Shugo Okamoto, Mariko Nishiwaki, Rika Takemoto, Hidemi Takeuchi, Jun Wada

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 ( 12 ) 2020.6

Risk Factors for Chronic Damage Accumulation Across Different Onset Eras in Systemic Lupus Erythematosus: A Cross-sectional Analysis of a Lupus Registry of Nationwide Institutions (LUNA) Reviewed

Keiji Ohashi, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu Asano, Yoshia Miyawaki, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori-Watanabe, Tomoko Kawabata, Nobuyuki Yajima, Jun Wada

ACTA MEDICA OKAYAMA 74 ( 3 ) 191 - 198 2020.6

Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report Reviewed

Yuriko Yamamura, Yoshinori Matsumoto, Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Toru Yamashita, Masahiro Yamamura, Ken-Ei Sada, Koji Abe, Jun Wada

BMC PULMONARY MEDICINE 20 ( 1 ) 2020.6

Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury Reviewed

Yizhen Sang, Kenji Tsuji, Akiko Inoue-Torii, Kazuhiko Fukushima, Shinji Kitamura, Jun Wada

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 ( 11 ) 2020.6

Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice Reviewed

Kazuhiko Fukushima, Shinji Kitamura, Kenji Tsuji, Yizhen Sang, Jun Wada

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 ( 11 ) 2020.6

Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials Reviewed

Kaethe Goossen, Monika Becker, Mark R. Marshall, Stefanie Buehn, Jessica Breuing, Catherine A. Firanek, Simone Hess, Hisanori Nariai, James A. Sloand, Qiang Yao, Tae Ik Chang, JinBor Chen, Ramon Paniagua, Yuji Takatori, Jun Wada, Dawid Pieper

AMERICAN JOURNAL OF KIDNEY DISEASES 75 ( 6 ) 830 - 846 2020.6

Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case report Reviewed

Katsuyuki Tanabe, Hiromitsu Kanzaki, Takahira Wada, Yuri Nakashima, Hitoshi Sugiyama, Hiroyuki Okada, Jun Wada

MEDICINE 99 ( 21 ) 2020.5

Targeting angiogenesis and lymphangiogenesis in kidney disease Reviewed

Katsuyuki Tanabe, Jun Wada, Yasufumi Sato

NATURE REVIEWS NEPHROLOGY 16 ( 5 ) 289 - 303 2020.5

The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study Reviewed

Akihiro Katayama, Atsuhito Tone, Mayu Watanabe, Sanae Teshigawara, Satoshi Miyamoto, Jun Eguchi, Atsuko Nakatsuka, Kenichi Shikata, Jun Wada

DIABETOLOGY INTERNATIONAL 11 ( 2 ) 97 - 104 2020.4

Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report Reviewed

Natsumi Matsuoka, Kenji Tsuji, Eiki Ichihara, Takayuki Hara, Kazuhiko Fukushima, Kishio Toma, Shinji Kitamura, Kenichi Inagaki, Hitoshi Sugiyama, Jun Wada

BMC NEPHROLOGY 21 ( 1 ) 2020.3

A novel homoplasmic mitochondrial DNA mutation (m.13376T>C, p.I347T) of MELAS presenting characteristic medial temporal lobe atrophy. Reviewed International journal

Ryo Sasaki, Yasuyuki Ohta, Noriko Hatanaka, Koh Tadokoro, Emi Nomura, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yoshio Omote, Eisaku Morimoto, Sanae Teshigawara, Jun Wada, Yu-Ichi Goto, Koji Abe

Journal of the neurological sciences 408 116460 - 116460 2020.1

Simultaneous development of IgA vasculitis and eosinophilic granulomatosis with polyangiitis. Reviewed International journal

Yosuke Asano, Yoshinori Matsumoto, Tatsuhiko Miyazaki, Akihiro Ishizu, Shin Morizane, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken-Ei Sada, Hirofumi Makino, Jun Wada

Modern rheumatology case reports 4 ( 1 ) 63 - 69 2020.1

Language：English Publishing type：Research paper (scientific journal)

Immunoglobulin A (IgA) vasculitis (IgAV) is a small vessel vasculitis presenting cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis caused by deposition of the IgA1-mediated immune complex. Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by eosinophil-rich and granulomatous inflammation in small to medium-sized vessels. Both IgAV and EGPA are classified as autoimmune systemic vasculitis, but the pathogenesis of immune complex-mediated IgAV and that of pauci-immune EGPA are different. Here we report a rare case of simultaneous development of IgAV and EGPA presenting palpable purpura and numbness in a patient with a history of asthma. Histological examination revealed leukocytoclastic vasculitis with deposition of IgA, IgM and C3 in the upper dermis and necrotising vasculitis with eosinophilic infiltration and granulomatous formation in the lower dermis and subcutaneous fat, indicating the existence of IgAV and EGPA. Our case provides evidence of concurrent development of two different types of vasculitis, which may affect disease-associated complications, therapeutic strategy and prognosis.

DOI： 10.1080/24725625.2019.1673528

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Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome Reviewed

Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Masashi Kitagawa, Keiko Tanaka, Yuzuki Kano, Koki Mise, Nozomu Otaka, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A. Uchida, Jun Wada

PLOS ONE 15 ( 1 ) 2020.1

Conditions, pathogenesis, and progression of diabetic kidney disease and early decliner in Japan Reviewed

Yui Yoshida, Kosuke Kashiwabara, Yosuke Hirakawa, Tetsuhiro Tanaka, Shinsuke Noso, Hiroshi Ikegami, Mitsuru Ohsugi, Kohjiro Ueki, Tomoya Mita, Hirotaka Watada, Daisuke Koya, Koki Mise, Jun Wada, Miho Shimizu, Takashi Wada, Yumi Ito, Ichiei Narita, Naoki Kashihara, Masaomi Nangaku, Yutaka Matsuyama

BMJ OPEN DIABETES RESEARCH & CARE 8 ( 1 ) 2020.1

Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome. Reviewed International journal

Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Masashi Kitagawa, Keiko Tanaka, Yuzuki Kano, Koki Mise, Nozomu Otaka, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A Uchida, Jun Wada

PloS one 15 ( 1 ) e0228337 2020

Language：English Publishing type：Research paper (scientific journal)

Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS.

DOI： 10.1371/journal.pone.0228337

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Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr/lpr Mice. Reviewed International journal

Sumie Hiramatsu-Asano, Katsue Sunahori-Watanabe, Sonia Zeggar, Eri Katsuyama, Tomoyuki Mukai, Yoshitaka Morita, Jun Wada

Frontiers in immunology 11 616141 - 616141 2020

Language：English Publishing type：Research paper (scientific journal)

Objective: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. Methods: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223 -/- Faslpr/lpr mice and the lupus phenotypes were analyzed. Results: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr /J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3' UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223 -/- Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8- cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223 +/+ Faslpr/lpr mice by flow cytometry. B6-Mir223 -/- Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. Conclusion: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.

DOI： 10.3389/fimmu.2020.616141

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Damage accrual related to pregnancies before and after diagnosis of systemic lupus erythematosus: a cross-sectional and nested case-control analysis from a lupus registry Reviewed

Morishita, M., Sada, K.-E., Ohashi, K., Miyawaki, Y., Asano, Y., Hayashi, K., Asano, S.H., Yamamura, Y., Watanabe, H., Narazaki, M., Matsumoto, Y., Kawabata, T., Yajima, N., Wada, J.

Lupus 29 ( 2 ) 2020

Robotic Renal Autotransplantation: A Feasibility Study in a Porcine Model Reviewed

Risa Kubota, Motoo Araki, Koichiro Wada, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Yuichi Ariyoshi, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Yuzuki Kano, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 74 ( 1 ) 53 - 58 2020

Letter to the Editor (Case report) Reviewed

Yuriko Yamamura, Yoshinori Matsumoto, Yosuke Asano, Yu Katayama, Keigo Hayashi, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Mariko Takano-Narazaki, Ken-Ei Sada, Jun Wada

RHEUMATOLOGY ADVANCES IN PRACTICE 4 ( 1 ) 2020

Immunomodulatory and regenerative effects of mesenchymal stem cell-derived extracellular vesicles in renal diseases

Tsuji, K., Kitamura, S., Wada, J.

International Journal of Molecular Sciences 21 ( 3 ) 2020

TREATMENT STATUS FOR OSTEOPOROSIS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: CROSS-SECTIONAL ANALYSIS FROM A LUPUS REGISTRY OF NATIONWIDE INSTITUTIONS (LUNA)

Jun Wada

Annals of the Rheumatic Diseases 2020

The Aging Population and Research into Treatments for Abdominal Aortic Aneurysms. Reviewed

Ryoko Umebayashi, Haruhito Adam Uchida, Jun Wada

Acta medica Okayama 73 ( 6 ) 475 - 477 2019.12

Language：English Publishing type：Research paper (scientific journal)

Abdominal aortic aneurysms (AAAs) usually expand asymptomatically until the occurrence of a life-threatening event such as aortic rupture, which is closely associated with high mortality. AAA and aortic dissection are ranked among the top 10 causes of death in Japan. The major risk factors for AAA are age over 65 years, male gender, family history, and smoking. Thus, for prevention, smoking cessation is the most important lifestyle-intervention. For treatment, since AAA generally affects elderly people, less invasive treatment is preferable. However, the only established treatment for AAA is open repair and endovascular repair. This review describes potential medical treatments to slow aneurysm growth or prevent AAA rupture.

DOI： 10.18926/AMO/57710

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HIV-associated Immune Complex Kidney Disease with C3-dominant Deposition Induced by HIV Infection after Treatment of IgA Nephropathy. Reviewed

Chieko Kawakita, Masaru Kinomura, Nozomu Otaka, Masashi Kitagawa, Hitoshi Sugiyama, Nobuchika Kusano, Masashi Mizuno, Jun Wada

Internal medicine (Tokyo, Japan) 58 ( 20 ) 3001 - 3007 2019.10

Language：English Publishing type：Research paper (scientific journal)

A 57-year-old man was diagnosed with IgA nephropathy. Hematuria and proteinuria were improved by tonsillectomy plus methylprednisolone pulse therapy. Lymphadenopathy, hypocomplementemia and pancytopenia were observed six years later, and urinalysis abnormalities recurred. A biopsy revealed mesangial proliferative glomerulonephritis with C3-dominant deposition. Human immunodeficiency virus (HIV) antibody demonstrated positive conversion. He was diagnosed with HIV-associated immune complex kidney disease (HIVICK). The hematuria, proteinuria and hypocomplementemia were improved by reducing the HIV viral load through antiretroviral therapy. When C3-dominant deposition is observed on a renal biopsy, HIVICK must be differentiated.

DOI： 10.2169/internalmedicine.2439-18

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Cluster Analysis Using Anti-Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis. Reviewed International journal

Keiji Ohashi, Ken-Ei Sada, Yu Nakai, Shun Matsushima, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori Watanabe, Tomoko Kawabata, Jun Wada

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 25 ( 6 ) 246 - 251 2019.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated. METHODS: Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters. RESULTS: Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2. CONCLUSIONS: Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.

DOI： 10.1097/RHU.0000000000000836

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Impaired mental health status in patients with chronic kidney disease is associated with estimated glomerular filtration rate decline. Reviewed International journal

Yasuhiro Onishi, Haruhito A Uchida, Hidemi Takeuchi, Yuki Kakio, Hitoshi Sugiyama, Jun Wada, Noriaki Shimada, Hironobu Tokumasu, Masaki Fukushima, Kenichiro Asano

Nephrology (Carlton, Vic.) 24 ( 9 ) 926 - 932 2019.9

Language：English Publishing type：Research paper (scientific journal)

AIM: Deteriorated health-related quality of life (HRQOL) is associated with increased risk for death in both chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients; however, the impact of HRQOL on CKD progression is not well investigated. METHODS: We aimed to evaluate the association between HRQOL and CKD progression in Japanese patients with CKD. One hundred and three outpatients who visited the department of nephrology at our hospital (mean estimated glomerular filtration rate (eGFR); 32.1 ± 11.2 mL/min per 1.73 m2 ) between April 2007 and March 2012 were enrolled in this study. The primary outcome was 30% decline of eGFR or ESRD. We assessed HRQOL of all participants at baseline, including the physical component summary (PCS), the mental component summary (MCS) and the role/social component summary (RCS), using SF-36. Based on the baseline score of PCS, MCS and RCS, we divided all subjects into two groups by median. RESULTS: We studied 66 men (64.1%) and 37 women aged 61.7 ± 10.0 years old. During approximately 2.5 years of follow-up period, 59 patients (57.3%) reached 30% eGFR decline or ESRD. Cox regression analyses demonstrated that lower MCS score was significantly associated with CKD progression (hazard ratio (HR) = 1.83, 95% CI = 1.04-3.21, P = 0.035), but that lower PCS score and RCS score were not (HR = 0.70, 95% CI = 0.39-1.25, P = 0.223; HR = 0.95, 95% CI = 0.54-1.67, P = 0.854, respectively). CONCLUSION: We found that impaired mental health was associated with CKD progression. The evaluation of the mental health should be performed in the patients with CKD.

DOI： 10.1111/nep.13515

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Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model. Reviewed International journal

Satoshi Tanimura, Katsuyuki Tanabe, Hiromasa Miyake, Kana Masuda, Keigo Tsushida, Tomoyo Morioka, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

American journal of physiology. Renal physiology 317 ( 2 ) F264-F274 - F274 2019.8

Language：English Publishing type：Research paper (scientific journal)

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/-) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/- mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/- mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

DOI： 10.1152/ajprenal.00045.2019

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Development of Hypertrophic Pachymeningitis in a Patient With Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis With Polyangiitis. Reviewed International journal

Yasuhiro Nakano, Yoshia Miyawaki, Ken-Ei Sada, Yuriko Yamamura, Yuzuki Kano, Keigo Hayashi, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Jun Wada

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 25 ( 5 ) e61 2019.8

A Patient with Type 3 Autoimmune Polyglandular Syndrome who Developed Systemic Lupus Erythematosus 8 years after the Diagnosis of Autoimmune Hepatitis. Reviewed

Tomoyo Mifune-Morioka, Haruhito A Uchida, Kazuhiko Fukushima, Mayu Watanabe, Chihiro Ouchi, Koki Mise, Chieko Kawakita, Yuzuki Kano, Akifumi Onishi, Kishio Toma, Jun Eguchi, Nozomu Wada, Fusao Ikeda, Erika Sasaki, Yu Suganami, Masayuki Kishida, Hitoshi Sugiyama, Hiroyuki Okada, Jun Wada

Acta medica Okayama 73 ( 4 ) 367 - 372 2019.8

Language：English Publishing type：Research paper (scientific journal)

Eight years prior to her present admission, a 61-year-old Japanese woman was diagnosed with autoimmune hepatitis, slowly progressive insulin-dependent diabetes mellitus, and chronic thyroiditis; she had been treated with oral prednisolone (PSL). After she suddenly discontinued PSL, she newly developed systemic lupus erythematosus. A combination therapy of oral PSL and intravenous cyclophosphamide resulted in remission. She was finally diagnosed with autoimmune polyglandular syndrome (APS) type 3 (3A ,3B, 3D), complicated with four different autoimmune diseases. Since patients with type 3 APS may present many manifestations over a long period of time, they should be carefully monitored.

DOI： 10.18926/AMO/56940

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Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease. Reviewed

Hironobu Toda, Haruhito Uchida, Kazufumi Nakamura, Hidemi Takeuchi, Masaru Kinomura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Jun Wada, Hiroshi Ito

Internal medicine (Tokyo, Japan) 58 ( 13 ) 1917 - 1922 2019.7

Language：English Publishing type：Research paper (scientific journal)

Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

DOI： 10.2169/internalmedicine.2076-18

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Capnocytophaga canimorsus peritonitis diagnosed by mass spectrometry in a diabetic patient undergoing peritoneal dialysis: a case report. Reviewed International journal

Katsuyuki Tanabe, Shugo Okamoto, Sumie Hiramatsu Asano, Jun Wada

BMC nephrology 20 ( 1 ) 219 - 219 2019.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Bacterial peritonitis is a serious complication of patients undergoing peritoneal dialysis (PD). Although the identification of causative organisms and use of appropriate antibiotics are essential for treatment, rare and fastidious bacteria are sometimes difficult to detect by conventional biochemical assays. Capnocytophaga canimorsus is a fastidious and slow-growing bacterium that forms a part of the normal oral flora of dogs and cats and is extremely rare as a peritonitis-causing organism. This report demonstrates the usefulness of a mass spectrometry-based technique in identifying such a rare organism in PD-related peritonitis and discusses the diagnosis and treatment of C. canimorsus peritonitis. CASE PRESENTATION: A 49-year-old woman with type 2 diabetes mellitus underwent PD for two years. Repeated exit-site infections led to subcutaneous pathway diversion two months ago. She was hospitalized with fever and abdominal pain as well as cloudy dialysis effluent. Laboratory data revealed increased serum C-reactive protein level and white blood cell (WBC) count in the effluent. Her exit site had no sign of infection, leading to the diagnosis of PD-related peritonitis. Initial therapy with intraperitoneal ceftazidime immediately ameliorated her symptoms, and the WBC count in the effluent normalized in five days. Culture test results of the dialysis effluent on admission were negative with no information regarding the infection route. However, mass spectrometry (MALDI Biotyper, Bruker Daltonics) successfully obtained the specific spectral pattern for C. canimorsus. She had four cats in her house and was advised not to allow the cats in the room where the bag exchange took place. CONCLUSIONS: C. canimorsus is a rare cause of peritonitis in PD patients and is usually susceptible to intraperitoneal third-generation cephalosporins. This mass spectrometry-based bacterial identification method could provide more opportunities to identify uncommon causes and promote appropriate antibiotics therapy in PD-related peritonitis.

DOI： 10.1186/s12882-019-1415-x

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Cavernous Transformation and Granulomatous Epididymis in Behçet Disease. Reviewed International journal

Yumi Motokura, Haruki Watanabe, Yuriko Yamamura, Yuzuki Kano, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 25 ( 4 ) 45 - 47 2019.6

Contrast-enhanced Computed Tomography-Guided Percutaneous Cryoablation of Renal Cell Carcinoma in a Renal Allograft: First Case in Asia. Reviewed

Ichiro Tsuboi, Motoo Araki, Hiroyasu Fujiwara, Toshihiro Iguchi, Takao Hiraki, Naoko Arichi, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Tomoko Sako, Atsushi Takamoto, Koichiro Wada, Yasuyuki Kobayashi, Toyohiko Watanabe, Hiroyuki Yanai, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Hiroaki Shiina, Susumu Kanazawa, Yasutomo Nasu

Acta medica Okayama 73 ( 3 ) 269 - 272 2019.6

Language：English

Nephron-sparing treatment should be offered whenever possible to avoid dialysis in allograph cases. Cryoablation is a new treatment option for treating small-sized renal cell cancer (RCCs). We report a case of RCC arising in a kidney allograft treated by cryoablation. To our knowledge, this is the first case in Asia of RCC in a renal allograft treated using cryoablation. Contrast-enhanced CT-guided percutaneous renal needle biopsy and cryoablation were used to identify the RCC, which could not be identified by other techniques. The postoperative course was uneventful. Contrast-enhanced CT also showed no recurrence or metastases at the 6-month follow-up.

DOI： 10.18926/AMO/56871

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Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet. Reviewed

Tomonari Kimura, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Kaoru Akazawa, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Daiji Miura, Jun Wada, Hiroshi Ito

International heart journal 60 ( 3 ) 728 - 735 2019.5

Language：English Publishing type：Research paper (scientific journal)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-β1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of β-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

DOI： 10.1536/ihj.18-392

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The clinical efficacy of angiotensin II type1 receptor blockers on inflammatory markers in patients with hypertension: a multicenter randomized-controlled trial; MUSCAT-3 study. Reviewed International journal

Ryoko Umebayashi, Haruhito A Uchida, Yuka Okuyama, Yuki Kakio, Yoshihisa Hanayama, Kenichi Shikata, Jun Wada

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 24 ( 3 ) 255 - 261 2019.5

Language：English Publishing type：Research paper (scientific journal)

Purpose: The purpose of present study was to evaluate the clinical efficacy of irbesartan on the anti-inflammatory and anti-oxidative stress effect in patients with hypertension compared to other ARBs. Further, we assessed the effect of the ARBs on kidney function and urinary albumin excretion. Methods: Eighty-five outpatients with hypertension who took an ARB except irbesartan more than 3 months were assigned into two groups, one continued the same ARB and the other switched the ARB to irbesartan for 6 months. Results: Although blood pressures were equally controlled (continue group: 148 ± 2/79 ± 2 mmHg to 131 ± 2/74 ± 2 mmHg; switch group: 152 ± 2/81 ± 2 mmHg to 132 ± 2/74 ± 2 mmHg; p < 0.001 each), the inflammatory markers (hsCRP, PTX3, MCP-1) and oxidative stress marker (MDA-LDL) did not change after 6 months in both groups. Urinary albumin excretion was significantly reduced only in the switch group without renal function deterioration (switch group 292.4 ± 857.9 mg/gCr to 250.6 ± 906.5 mg/gCr, p = 0.012). Conclusion: These results provide knowledge of the characteristics of irbesartan, suggesting appropriate choice of ARBs in the treatment for hypertension should be considered.

DOI： 10.1080/1354750X.2018.1548033

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Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Reviewed International journal

Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Fumika Nanto-Hara, Jiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching-Chin Yang, Chitose Suzuki, Matthew C Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

Nature communications 10 ( 1 ) 1835 - 1835 2019.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Communications

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

DOI： 10.1038/s41467-019-09735-4

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Parathyroid Lipoadenoma: A Pitfall in Preoperative Localization. Reviewed

Satoshi Fujisawa, Kenichi Inagaki, Jun Wada

Internal medicine (Tokyo, Japan) 58 ( 8 ) 1183 - 1184 2019.4

Exogenous Vasohibin-2 Exacerbates Angiotensin II-Induced Ascending Aortic Dilation in Mice. Reviewed

Michihiro Okuyama, Haruhito A Uchida, Yoshiko Hada, Yuki Kakio, Nozomu Otaka, Ryoko Umebayashi, Katsuyuki Tanabe, Yasuhiro Fujii, Shingo Kasahara, Venkateswaran Subramanian, Alan Daugherty, Yasufumi Sato, Jun Wada

Circulation reports 1 ( 4 ) 155 - 161 2019.4

Language：English Publishing type：Research paper (scientific journal)

Background: Chronic angiotensin II (AngII) infusion promotes ascending aortic dilation in C57BL/6J mice. Meanwhile, vasohibin-2 (VASH2) is an angiogenesis promoter in neovascularization under various pathologic conditions. The aim of this study was to investigate whether exogenous VASH2 influences chronic AngII-induced ascending aortic dilation. Methods and Results: Eight-ten-week-old male C57BL/6J mice were injected with adenovirus (Ad) expressing either VASH2 or LacZ. One week after the injection, mice were infused with either AngII or saline s.c. for 3 weeks. Mice were divided into 4 groups: AngII+VASH2, AngII+LacZ, saline+VASH2, and saline+LacZ. Overexpression of VASH2 significantly increased AngII-induced intimal areas as well as the external diameter of the ascending aorta. In addition, VASH2 overexpression promoted ascending aortic medial elastin fragmentation in AngII-infused mice, which was associated with increased matrix metalloproteinase activity and medial smooth muscle cell (SMC) apoptosis. On western blot analysis, accumulation of apoptotic signaling proteins, p21 and p53 was increased in the AngII+VASH2 group. Furthermore, transfection of human aortic SMC with Ad VASH2 increased p21 and p53 protein abundance upon AngII stimulation. Positive TUNEL staining was also detected in the same group of the human aortic SMC. Conclusions: Exogenous VASH2 exacerbates AngII-induced ascending aortic dilation in vivo, which is associated with increased medial apoptosis and elastin fragmentation.

DOI： 10.1253/circrep.CR-19-0008

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The relationship between repeated measurement of casual and 24-h urinary sodium-to-potassium ratio in patients with chronic kidney disease. Reviewed International journal

Yuka Okuyama, Haruhito A Uchida, Toshiyuki Iwahori, Hiroyoshi Segawa, Ayako Kato, Hidemi Takeuchi, Yuki Kakio, Ryoko Umebayashi, Masashi Kitagawa, Hitoshi Sugiyama, Katsuyuki Miura, Hirotsugu Ueshima, Jun Wada

Journal of human hypertension 33 ( 4 ) 286 - 297 2019.4

Language：English Publishing type：Research paper (scientific journal)

This study aimed to clarify the relationship between repeated measurements of casual (spot) and 24-h urinary sodium-to-potassium (Na/K) ratios in patients with chronic kidney disease (CKD). A total of 61 inpatients with CKD, 31 in stage 1-3 (eGFR [estimated glomerular filtration rate] ≥ 30 ml/min/1.73 m2) and 30 in stage 4-5 (eGFR < 30 ml/min/1.73 m2), aged 20-85 consuming a low-sodium diet (NaCl [sodium chloride] 6 g/day) were recruited. Urinary Na, K, and Na/K ratios were measured in both casual urine samples and 2-day, 24 h urine samples, and then analyzed by correlation and Bland-Altman analyses. Mean 24-h urine Na/K ratio was higher in participants in stage 4-5 (5.1) than in participants in stage 1-3 (4.1) CKD. Casual urine Na/K ratio was strongly correlated with 2-day, 24-h urine Na/K ratio by sampling 4 casual urine specimens every morning and evening in participants in stage 1-3 (r = 0.69-0.78), but not in stage 4-5 (r = 0.12-0.19). The bias for mean Na/K ratio between 2-day, 24-h urine, and the 4 casual urine sampling ranged from -0.86 to 0.16 in participants in stage 1-3, and the quality of agreement for the mean of this casual urine sampling was similar to that of sampling 8 casual urine samples for estimating 2-day, 24-h values. Methods using repeated casual urine Na/K ratios may provide a reasonable estimation of 24-h urine Na/K ratio in normotensive and hypertensive as well as individuals with stage 1-3, but not stage 4-5 CKD.

DOI： 10.1038/s41371-018-0127-1

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Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells. Reviewed International journal

Satoshi Fujisawa, Motoshi Komatsubara, Kanako Ogura-Ochi, Naoko Tsukamoto-Yamauchi, Kishio Toma, Kenichi Inagaki, Jun Wada, Fumio Otsuka

Peptides 113 35 - 40 2019.3

Language：English Publishing type：Research paper (scientific journal)

The impact of orexins on anterior pituitary function has yet to be clarified. We studied the effects of orexin A and its interaction with the bone morphogenetic protein (BMP) system on the regulatory role of prolactin synthesis using rat lactotrope GH3 cells expressing BMP-4. Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells. Orexin A suppressed forskolin-induced, but not basal, prolactin mRNA expression without reducing cAMP levels. Of note, orexin A suppressed BMP-4-induced prolactin mRNA and cAMP synthesis. Impairment of the effects of orexin by chemical inhibitors suggested involvement of the P38 pathway in the OX1R activity that suppresses BMP-4-induced PRL expression. Given that inhibition of BMP-receptor signaling reduced prolactin mRNA levels, endogenous BMP action is likely to be linked to the activation of prolactin synthesis by GH3 cells. Orexin A was revealed to suppress Smad1/5/9 phosphorylation and Id-1 transcription induced by BMP-4, which was restored in the presence of orexin-receptor antagonists, suggesting that the inhibitory effect of orexin A occurred via OX1R. Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression. These results indicated that orexin A plays an inhibitory role in prolactin production through suppression of endogenous BMP activity in GH3 cells, suggesting that a new functional role of the interaction between orexin and BMP-4 is modulation of prolactin levels in lactotrope cells.

DOI： 10.1016/j.peptides.2019.01.002

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Regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice derived CD4+ T cells. Reviewed International journal

Sumie Hiramatsu, Katsue S Watanabe, Sonia Zeggar, Yosuke Asano, Yoshia Miyawaki, Yuriko Yamamura, Eri Katsuyama, Takayuki Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

Scientific reports 9 ( 1 ) 3054 - 3054 2019.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Nature

Global DNA hypomethylation in CD4+ cells in systemic lupus erythematosus (SLE) was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and Ctse mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was 93.3 ± 2.05% methylated in B6 mice, while 80.0 ± 6.2% methylated and mutated to CGGG in MRL mice. Kaiso is known to bind to mCGCG and we hypothesized that it represses expression of Ctse in B6 mice. The binding of Kaiso to mCGCG site in B6 mice was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or Trichostatin A showed the suppression of binding of Kaiso to mCGCG motif by ChIP-PCR and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.

DOI： 10.1038/s41598-019-38809-y

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Effect of an enhanced recovery after surgery protocol in patients undergoing pancreaticoduodenectomy: A randomized controlled trial. Reviewed International journal

Kosei Takagi, Ryuichi Yoshida, Takahito Yagi, Yuzo Umeda, Daisuke Nobuoka, Takashi Kuise, Shiro Hinotsu, Takashi Matsusaki, Hiroshi Morimatsu, Jun Eguchi, Jun Wada, Masuo Senda, Toshiyoshi Fujiwara

Clinical nutrition (Edinburgh, Scotland) 38 ( 1 ) 174 - 181 2019.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND & AIMS: Evidence of the advantages of enhanced recovery after surgery (ERAS) protocols following pancreaticoduodenectomy (PD) is limited. The aim of this study was to examine the efficiency of ERAS protocols in patients following PD. METHODS: Between June 2014 and October 2016, patients undergoing PD were randomly assigned to receive ERAS protocols or standard care. The primary endpoint was the postoperative length of stay. Secondary endpoints included postoperative complications, postoperative quality-of-life (QoR-40J), readmission, and medical cost. RESULTS: Of 80 eligible patients, 74 were analyzed in intention-to-treat principles: 37 in the control group and 37 in the ERAS group. The mean length of stay in the ERAS group was significantly shorter than that in the control group (20.1 ± 5.4 vs 26.9 ± 13.5 days, P < 0.001). The ERAS group had a significantly lower percentage of postoperative complications (32.4% vs 56.8%, P = 0.034) and readmissions (0% vs 8.1%, P = 0.038). Quality-of-life was also significantly better in the ERAS group (184 ± 12.4 vs 177 ± 14.5, P = 0.022). The total medical cost was lower in the ERAS group, but not significantly ($25,445 ± 5065 vs $28,384 ± 9999, P = 0.085). CONCLUSIONS: The optimization of ERAS protocols in patients undergoing PD is safe and accelerates perioperative recovery and quality-of-life, thereby reducing the length of stay. Morbidity was significantly decreased in the ERAS group without compromising surgical outcome. REGISTRATION NUMBER: UMIN000014068.

DOI： 10.1016/j.clnu.2018.01.002

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Risk factors for cytomegalovirus infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Reviewed International journal

Michiko Morishita, Ken-Ei Sada, Yoshinori Matsumoto, Keigo Hayashi, Yosuke Asano, Sumie Hiramatsu Asano, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Haruki Watanabe, Tomoko Kawabata, Jun Wada

PloS one 14 ( 7 ) e0218705 2019

Language：English Publishing type：Research paper (scientific journal)

AIMS: Cytomegalovirus (CMV) infection under immunosuppression sometimes causes death. This study aimed to elucidate risk factors for CMV infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Patients with AAV who underwent remission induction treatment at Okayama University Hospital between 2006 and 2016 were retrospectively analyzed. The primary outcome was the development of CMV infection within 3 months. RESULTS: Of the 111 patients, 13 (11.7%) patients developed CMV infection. Patients with CMV infection were older (p = 0.030) and had a higher body mass index (p = 0.029) in comparison to those without CMV infection. A higher proportion had a severe form (p = 0.001) and granulomatosis with polyangiitis (GPA) (p = 0.001), as well as a higher Birmingham Vasculitis Activity Score (p = 0.018) and C-reactive protein (p = 0.018) levels at baseline. Using logistic regression analysis, severe form and GPA were independent risk factors (odds ratio [OR] = 9.68, 95% confidence interval [CI] = 1.92-60.23, and OR = 7.46, 95% CI = 1.46-47.60, respectively). In addition, patients with CMV infection were more likely than those without infection to be glucocorticoid-related diabetes mellitus (p = 0.025). CONCLUSION: Our study highlights disease severity and subgroups of AAV as risk factors for CMV infection.

DOI： 10.1371/journal.pone.0218705

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Report of health checkup system for chronic kidney disease in general population in Okayama city: effect of health guidance intervention on chronic kidney disease outcome. Reviewed International journal

Yuki Kakio, Haruhito A Uchida, Hidemi Takeuchi, Yuka Okuyama, Ryoko Umebayashi, Hiroyuki Watatani, Yohei Maeshima, Hitoshi Sugiyama, Jun Wada

International journal of nephrology and renovascular disease 12 143 - 152 2019

Language：English Publishing type：Research paper (scientific journal)

Background: From 2011, Okayama municipal government started the health checkup follow-up project to find those who were unaware of suffering chronic kidney disease and to prevent from aggravation of CKD stage. In this study, we aimed to evaluate the effect of 2 years' CKD-follow-up project regarding renal function and CKD risks. Patients and methods: Those who received a health checkup by the national health insurance in Okayama city in 2011 were recruited. The patients with lifestyle-related diseases or metabolic syndrome were excluded. Subjects who had an estimated glomerular filtration rate<50 mL/min/1.73 m2 or urinary protein positive by dipstick test were defined as compromised renal function group. They were recommended to visit a medical institution. Non-compromised renal function participants with two or more risks for CKD (hyperglycemia, higher blood pressure, dyslipidemia, hyperuricemia) were recommended to receive a health guidance (risk group). The change of renal function and CKD risks between 2011 and 2013 in each group was examined. Results: A total of 28,309 people received a health checkup in 2011. In compromised renal function group, 39.5% (96/243) of the subjects improved their CKD stages in 2013 regardless of the visit of medical institutions or the frequency of receiving health checkup. In risk group, 63.4% (260/410) of the subjects decreased their CKD risks in 2013 independent of the reception of health guidance. Conclusion: In both compromised renal function group and risk group, more than half of subjects kept their kidney function (217/243) and decreased the number of CKD risks (260/410) in 2 years' follow-up. Receiving a health checkup itself and notification of one's own health condition could exert a protective effect on kidney function.

DOI： 10.2147/IJNRD.S198781

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Thrombocytosis as a prognostic factor in polymyalgia rheumatica: characteristics determined from cluster analysis. Reviewed International journal

Keigo Hayashi, Keiji Ohashi, Haruki Watanabe, Ken-Ei Sada, Kenta Shidahara, Yosuke Asano, Sumie Hiramatsu Asano, Yuriko Yamamura, Yoshia Miyawaki, Michiko Morishita, Yoshinori Matsumoto, Tomoko Kawabata, Jun Wada

Therapeutic advances in musculoskeletal disease 11 1759720X19864822 2019

Language：English Publishing type：Research paper (scientific journal)

Background: This study aimed to identify the clinical subgroups of polymyalgia rheumatica (PMR) using cluster analysis and compare the outcomes among the identified subgroups. Methods: We enrolled patients with PMR who were diagnosed at Okayama University Hospital, Japan between 2006 and 2017, met the 2012 European League Against Rheumatism/American College of Rheumatology provisional classification criteria for PMR, and were treated with glucocorticoids. Hierarchical cluster analysis using variables selected by principal component analysis was performed to identify the clusters. Subsequently, the outcomes among the identified clusters were compared in the study. The primary outcome was treatment response at 1 month after commencement of treatment. The secondary outcome was refractory clinical course, which was defined as the requirement of additional treatments or relapse during a 2-year observational period. Results: A total of 61 consecutive patients with PMR were enrolled in the study. Their mean age was 71 years, and 67% were female. Hierarchical cluster analysis revealed three distinct subgroups: cluster 1 (n = 14) was characterized by patients with thrombocytosis (all patients showed a platelet count of >45 × 10⁴/µl), cluster 2 (n = 38), by patients without peripheral arthritis, and cluster 3 (n = 9), by patients with peripheral arthritis. The patients in cluster 1 achieved treatment response less frequently than those in cluster 2 (14% versus 47%, p = 0.030). Refractory cases were more frequent in cluster 1 than in cluster 2; however, no significant difference was noted (71% versus 42%, p = 0.06). Conclusions: Thrombocytosis could predict the clinical course in patients with PMR.

DOI： 10.1177/1759720X19864822

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Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease. Reviewed International journal

Akifumi Onishi, Hitoshi Sugiyama, Masashi Kitagawa, Toshio Yamanari, Keiko Tanaka, Ayu Ogawa-Akiyama, Yuzuki Kano, Koki Mise, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A Uchida, Jun Wada

Disease markers 2019 5432453 - 5432453 2019

Language：English Publishing type：Research paper (scientific journal)

Background: Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2'-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD. Method: We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 years, male: 53.2%, and glomerulonephritis: 51.0%) using a competitive enzyme-linked immunosorbent assay and investigated the relationships among urine 5MedC, urine albumin, urine α1-microglobulin (α1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner. Results: The urine 5MedC level was significantly increased in the later stages of CKD compared to the early to middle stages of CKD. In multiple logistic regression models, urine 5MedC was significantly associated with the prediction of later CKD stages. Urine 5MedC (median value, 65.9 μmol/gCr) was significantly able to predict a 30% decline in the estimated GFR or a development of end-stage renal disease when combined with macroalbuminuria or an increased level of urine α1MG (median value, 5.7 mg/gCr). Conclusion: The present data demonstrate that the urine 5MedC level is associated with a reduced renal function and can serve as a novel and potent biomarker for predicting the renal outcome in CKD patients. Further studies will be necessary to elucidate the role of urine DNA methylation in the progression of CKD.

DOI： 10.1155/2019/5432453

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Hemoptysis Originating from the Bronchial Artery in Takayasu Arteritis with Ulcerative Colitis

Jun Wada

Internal Medicine 2019

OPTIMAL INITIAL DOSE OF GLUCOCORTICOID FOR ELDERLY-ONSET ANCA ASSOCIATED VASCULITIS: SAFTY OUTOCOME ANALYSIS OF TWO NATIONWIDE, PROSPECTIVE, INCEPTION COHORT STUDIES

Jun Wada

Annals of the Rheumatic Diseases 2019

Exogenous Vasohibin-2 Influences Development of Angiotensin II-induced Ascending Aortic Aneurysms but Not Abdominal Aortic Aneurysms in Either Normolipidemic or Apolipoprotein E-Deficient Mice

Jun Wada

Arteriosclerosis, Thrombosis, and Vascular Biology 2019

DOSE-DEPENDENT RISK OF METHOTREXATE FOR RENAL IMPAIRMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS

Jun Wada

Annals of the Rheumatic Diseases 2019

Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. Reviewed International journal

Yusuke Shibata, Atsuko Nakatsuka, Jun Eguchi, Satoshi Miyamoto, Yukari Masuda, Motoharu Awazawa, Akinobu Takaki, Ryuichi Yoshida, Takahito Yagi, Jun Wada

Journal of medical case reports 12 ( 1 ) 368 - 368 2018.12

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Acquired partial lipoatrophy has been reported after bone marrow transplantation during childhood; however, no adult cases have previously been reported. We herein report two adult cases of acquired partial lipoatrophy after transplantation. CASE PRESENTATION: A 28-year-old Japanese woman developed diabetic ketoacidosis and received insulin therapy after bone marrow transplantation. She manifested partial lipoatrophy of the extremities, prominent insulin resistance, hyperglycemia, hypertriglyceridemia, and fatty liver. A 40-year-old Japanese woman underwent liver transplantation from a living donor for alcoholic liver disease after abstinence from alcohol. She newly developed non-alcoholic steatohepatitis and diabetes. Non-alcoholic steatohepatitis progressed to liver failure, and a second liver transplantation from a brain-dead donor was performed at 42 years of age. She demonstrated loss of subdermal fat of the upper and lower extremities, prominent insulin resistance, hyperglycemia, and hypertriglyceridemia. In both cases, the injection of recombinant methionyl human leptin reversed all of the metabolic abnormalities. CONCLUSIONS: Acquired partial lipoatrophy after transplantation is a manifestation of chronic graft-versus-host disease in adults. This entity is associated with diabetes with prominent insulin resistance and severe hypertriglycemia and can be successfully treated with metreleptin for the long term.

DOI： 10.1186/s13256-018-1901-y

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Antineutrophil cytoplasmic antibody-positive familial Mediterranean fever and hyperthyroidism: A case report. International journal

Sorato Segoe, Ken-Ei Sada, Keigo Hayashi, Yuriko Yamamura, Michiko Morishita, Haruki Watanabe, Yoshinori Matsumoto, Jun Wada

Medicine 97 ( 51 ) e13805 2018.12

Language：English Publishing type：Research paper (scientific journal)

RATIONALE: Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder characterized by serositis and recurrent fever. Previous reports identified patients with antineutrophil cytoplasmic antibody (ANCA)-positive FMF, but vasculitis symptoms were not reported. PATIENT CONCERNS: We report the case of a 44-year-old man with numbness. He had a history of 3 episodes of pleurisy and was being treated with propylthiouracil for hyperthyroidism. Because he was ANCA-positive, we suspected drug-induced ANCA-associated vasculitis and propylthiouracil was discontinued. However, his numbness was not ameliorated, and he again developed high fever with pleurisy. DIAGNOSIS: Diagnosis of FMF was finally made, and genetic analysis revealed compound heterozygous mutations in exon 2 of the familial Mediterranean fever gene (L110P/E148Q). INTERVENTIONS: The patient was treated with 0.5 mg/day of colchicine. OUTCOMES: His numbness improved, and fever has not recurred. LESSONS: Appearance of ANCA and development of vasculitis should be considered in a clinical course of FMF with hyperthyroidism.

DOI： 10.1097/MD.0000000000013805

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Diabetic nephropathy is associated with frailty in patients with chronic hemodialysis. Reviewed

Yuki Kakio, Haruhito A Uchida, Hidemi Takeuchi, Yuka Okuyama, Michihiro Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Shingo Kasahara, Jun Wada

Geriatrics & gerontology international 18 ( 12 ) 1597 - 1602 2018.12

Language：English Publishing type：Research paper (scientific journal)

AIM: Since 1998, the leading cause of chronic hemodialysis in Japan has been diabetic nephropathy. Diabetes mellitus is known to be a risk factor for frailty, but it still remains unknown whether diabetic nephropathy is associated with frailty in chronic dialysis patients. The authors carried out the present study to reveal the association between frailty and diabetic nephropathy in chronic hemodialysis patients. METHODS: A total of 355 patients who were on hemodialysis were recruited. Participants were divided into two groups of either patients who suffered diabetic nephropathy with end-stage renal disease (DN group, n = 150) or not (Non-DN group, n = 205). The authors investigated the difference of the prevalence of frailty between the two groups. Furthermore, the authors examined the risk factors for frailty. RESULTS: The prevalence of frailty in the DN group was significantly higher than that in the Non-DN group (28.0% vs 16.5%, P = 0.0161). To evaluate the association between frailty and its risk factors, we compared frail patients (n = 71) and non-frail patients (n = 262). After adjusting their interrelationships by using multivariate logistic regression analysis, diabetic nephropathy was determined as a significant risk factor for frailty. CONCLUSIONS: The authors found the close association between frailty and diabetic nephropathy in chronic hemodialysis patients. Geriatr Gerontol Int 2018; 18: 1597-1602.

DOI： 10.1111/ggi.13534

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Other Link： http://orcid.org/0000-0001-6508-4338

Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus Reviewed

Miyawaki, Y., Sada, K., Asano, Y., Hayashi, K., Yamamura, Y., Hiramatsu, S., Ohashi, K., Morishita, M., Watanabe, H., Matsumoto, Y., Kawabata, T., Wada, J.

Lupus 27 ( 13 ) 2093 2018.11

An open-label pilot study on preventing glucocorticoid-induced diabetes mellitus with linagliptin. Reviewed International journal

Yoshia Miyawaki, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Yoshinori Matsumoto, Katsue Sunahori-Watanabe, Tomoko Kawabata, Jun Wada

Journal of medical case reports 12 ( 1 ) 288 - 288 2018.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Numerous patients develop diabetes in response to glucocorticoid therapy. This study explored the efficacy, safety, and preventive potential of the dipeptidyl peptidase-4 inhibitor, linagliptin (TRADJENTA®), in the development of glucocorticoid-induced diabetes mellitus. METHODS: From December 2014 to November 2015, we recruited non-diabetic Japanese patients scheduled for treatment with daily prednisolone ≥20 mg. Enrolled patients had at least one of following risk factors for glucocorticoid-induced diabetes mellitus: estimated glomerular filtration rate ≤ 60 mL/minute/1.73 m2; age ≥ 65 years; hemoglobin A1c > 6.0%. A daily dose of 5 mg of linagliptin was administered simultaneously with glucocorticoid therapy. The primary outcome was the development of glucocorticoid-induced diabetes mellitus. Additional orally administered hypoglycemic medications and/or insulin injection therapy was initiated according to the blood glucose level. RESULTS: Four of five patients developed glucocorticoid-induced diabetes mellitus within 1 week of glucocorticoid treatment. For 12 weeks, two of the four patients with glucocorticoid-induced diabetes mellitus required orally administered medications, but no patients required insulin. Blood glucose levels before breakfast and lunch tended to decrease with time; the median glucose levels before breakfast were 93 and 79.5 mg/dL at 1 and 3 weeks, respectively. Two patients experienced mild hypoglycemia around 2 weeks. Glucose levels after lunch remained high throughout all 4 weeks despite decreasing the glucocorticoid dosage. CONCLUSIONS: Linagliptin may be insufficient to prevent the development of glucocorticoid-induced diabetes mellitus but has the potential to reduce the requirement for insulin injection therapy. Treatment of glucocorticoid-induced diabetes mellitus was continued for at least 1 month and fasting hypoglycemia in early morning should be monitored after 2 weeks. TRIAL REGISTRATION: This trial was registered 02 November 2014 with UMIN Clinical Trials Registry (no. 000015588 ).

DOI： 10.1186/s13256-018-1817-6

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Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy. Reviewed International journal

Keiko Tanaka, Hitoshi Sugiyama, Toshio Yamanari, Koki Mise, Hiroshi Morinaga, Masashi Kitagawa, Akifumi Onishi, Ayu Ogawa-Akiyama, Katsuyuki Tanabe, Jun Eguchi, Yasukazu Ohmoto, Kenichi Shikata, Jun Wada

Nephrology (Carlton, Vic.) 23 ( 9 ) 855 - 862 2018.9

Language：English Publishing type：Research paper (scientific journal)

AIM: Trefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN). METHODS: We investigated the renal mRNA expression of TFF3 by real-time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively. RESULTS: The renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients. CONCLUSION: Renal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.

DOI： 10.1111/nep.13444

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Chronic kidney disease is associated with carotid atherosclerosis and symptomatic ischaemic stroke. Reviewed International journal

Nobuo Kajitani, Haruhito A Uchida, Isao Suminoe, Yuki Kakio, Masashi Kitagawa, Hajime Sato, Jun Wada

The Journal of international medical research 46 ( 9 ) 3873 - 3883 2018.9

Language：English Publishing type：Research paper (scientific journal)

Objective We aimed to investigate the relationships among chronic kidney disease (CKD), symptomatic ischaemic stroke, and carotid atherosclerosis. Methods We enrolled 455 patients who underwent carotid ultrasonography in our hospital, including 311 patients with symptomatic ischaemic stroke and 144 patients without symptomatic ischaemic stroke. Carotid intima-media thickness (IMT), the rate of internal carotid artery stenosis, and maximal plaque size were evaluated. Results The mean age of the patients was 68.5 ± 11.0 years and the mean estimated glomerular filtration rate (eGFR) was 68.8 ± 18.2 mL/min/1.73 m2. After adjustment for cardiovascular risk factors, the mean IMT was significantly higher in patients with CKD than in those without CKD. The IMT and eGFR were negatively correlated in patients with stroke (r = -0.169). Multiple logistic regression analyses showed that mean IMT, plaque size, and internal carotid artery stenosis were significant determinants of symptomatic ischaemic stroke after adjustment of multivariate risk factors. Furthermore, the eGFR was a negative determinant of symptomatic ischaemic stroke after adjusting for classical risk factors (odds ratio [95% confidence interval] = 0.868 [0.769-0.979]). Conclusion CKD might be associated with the carotid atherosclerosis and symptomatic ischaemic stroke.

DOI： 10.1177/0300060518781619

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Peripheral artery disease is associated with frailty in chronic hemodialysis patients. Reviewed International journal

Michihiro Okuyama, Hidemi Takeuchi, Haruhito A Uchida, Yuki Kakio, Yuka Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Shingo Kasahara, Jun Wada

Vascular 26 ( 4 ) 425 - 431 2018.8

Language：English Publishing type：Research paper (scientific journal)

Objectives The clinical condition of frailty is a common problem in the elderly population. However, the relationship between peripheral artery disease and frailty in hemodialysis patients remains unknown. The aim of this study was to identify the relationships between peripheral artery disease and frailty in Japanese chronic hemodialysis patients. Methods A total of 362 chronic hemodialysis patients who regularly visited six institutions were enrolled. To evaluate frailty, the modified Fried's frailty phenotype adjusted for Japanese were used. Peripheral artery disease was defined as ankle-brachial index <0.9. Results Of 362 patients, 62 patients (17.1%) were categorized as peripheral artery disease group and 300 patients (82.9%) as Non-peripheral artery disease group. The prevalence of frailty in the peripheral artery disease group was significantly higher than in the Non-peripheral artery disease group (34% vs. 18%, P = 0.0103). Non-shunt side grip strength was significantly stronger in the Non-peripheral artery disease group (23.6 kg vs. 17.0 kg, P < 0.0001). Thigh circumferences were also significantly larger in the Non-peripheral artery disease group (41.7 cm vs. 39.7 cm, P = 0.0054). A multivariate logistic regression analysis demonstrated that the factors independently associated with peripheral artery disease were as follows: frailty (odds ratio = 2.06, 95% confidence interval 1.09-3.89) and myocardial infarction (odds ratio = 3.74, 95% confidence interval 2.05-6.83). Conclusions It is concluded that peripheral artery disease is closely associated with frailty in hemodialysis patients.

DOI： 10.1177/1708538118756690

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Identification of Novel Urinary Biomarkers for Predicting Renal Prognosis in Patients With Type 2 Diabetes by Glycan Profiling in a Multicenter Prospective Cohort Study: U-CARE Study 1. Reviewed International journal

Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Sanae Teshigawara, Atsuhito Tone, Haruhito A Uchida, Jun Eguchi, Atsuko Nakatsuka, Daisuke Ogawa, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

Diabetes care 41 ( 8 ) 1765 - 1775 2018.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Because quantifying glycans with complex structures is technically challenging, little is known about the association of glycosylation profiles with the renal prognosis in diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: In 675 patients with type 2 diabetes, we assessed the baseline urinary glycan signals binding to 45 lectins with different specificities. The end point was a decrease of estimated glomerular filtration rate (eGFR) by ≥30% from baseline or dialysis for end-stage renal disease. RESULTS: During a median follow-up of 4.0 years, 63 patients reached the end point. Cox proportional hazards analysis revealed that urinary levels of glycans binding to six lectins were significantly associated with the outcome after adjustment for known indicators of DKD, although these urinary glycans, except that for DBA, were highly correlated with baseline albuminuria and eGFR. Hazard ratios for these lectins were (+1 SD for the glycan index) as follows: SNA (recognizing glycan Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 1.32 (1.04-1.67). Adding these glycan indexes to a model containing known indicators of progression improved prediction of the outcome (net reclassification improvement increased by 0.51 [0.22-0.80], relative integrated discrimination improvement increased by 0.18 [0.01-0.35], and the Akaike information criterion decreased from 296 to 287). CONCLUSIONS: The urinary glycan profile identified in this study may be useful for predicting renal prognosis in patients with type 2 diabetes. Additional investigation of glycosylation changes and urinary glycan excretion in DKD is needed.

DOI： 10.2337/dc18-0030

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Refractory neuromyelitis optica spectrum disorder in systemic lupus erythematosus successfully treated with rituximab Reviewed

K. Shidahara, K. Hayashi, K. E. Sada, S. Hiramatsu, M. Morishita, H. Watanabe, Y. Matsumoto, T. Kawabata, J. Wada

Lupus 27 ( 8 ) 1374 - 1377 2018.7

Role of Lgals9 Deficiency in Attenuating Nephritis and Arthritis in BALB/c Mice in a Pristane-Induced Lupus Model. Reviewed International journal

Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada

Arthritis & rheumatology (Hoboken, N.J.) 70 ( 7 ) 1089 - 1101 2018.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvement, the development of lupus nephritis determines prognosis, and arthritis impairs quality of life. Galectin 9 (Gal-9, Lgals9) is a β-galactoside-binding lectin that has been used for clinical application in autoimmune diseases, since recombinant Gal-9, as a ligand for T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), induces apoptosis of activated CD4+TIM-3+ Th1 cells. This study was undertaken to investigate whether deficiency of Lgals9 has beneficial or deleterious effects on lupus in a murine model. METHODS: Gal-9+/+ and Gal-9-/- female BALB/c mice were injected with pristane, and the severity of arthritis, proteinuria, and levels of autoantibody production were assessed at several time points immediately following injection. At 7 months after pristane injection, renal pathologic features, the severity of joint inflammation, and formation of lipogranulomas were evaluated. Subsets of inflammatory cells in the spleen and peritoneal lavage were characterized, and expression levels of cytokines from peritoneal macrophages were analyzed. RESULTS: Lgals9 deficiency protected against the development of immune complex glomerulonephritis, arthritis, and peritoneal lipogranuloma formation in BALB/c mice in this murine model of pristane-induced lupus. The populations of T cell subsets and B cells in the spleen and peritoneum were not altered by Lgals9 deficiency in pristane-injected BALB/c mice. Furthermore, Lgals9 deficiency protected against pristane-induced lupus without altering the Toll-like receptor 7-type I interferon pathway. CONCLUSION: Gal-9 is required for the induction and development of lupus nephritis and arthritis in this murine model of SLE. The results of the current investigation provide a potential new strategy in which antagonism of Gal-9 may be beneficial for the treatment of nephritis and arthritis in patients with SLE through targeting of activated macrophages.

DOI： 10.1002/art.40467

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Development of a novel estimation method for hemoglobin A1c using glycated albumin in type 2 diabetes mellitus patients with end-stage renal disease. Reviewed

Akihiko Nakamura, Ryo Kodera, Noriko Sakamoto, Haruyo Ujike, Jun Wada, Kenichi Shikata, Hirofumi Makino

Diabetology international 9 ( 3 ) 179 - 188 2018.7

Language：English Publishing type：Research paper (scientific journal)

Aim: We developed a novel estimation method for hemoglobin A1c (HbA1c) in type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). This method is based on the glycated albumin (GA) level. Methods: Of the 788 Japanese patients with T2D included in this study, 545 had normal renal function (NRF group) and 243 had ESRD. Oral glucose tolerance tests (OGTTs) were performed in 80 subjects. The variables GA, body mass index (BMI), hemoglobin (Hb), and estimated glomerular filtration rate (eGFR) were significantly associated with the GA-to-HbA1c ratio and were used to determine the estimated HbA1c (eHbA1c). One method of estimating HbA1c involved dividing GA by the GA-to-HbA1c ratio predicted from the estimated regression equation; the estimated HbA1c obtained in this manner was denoted eHbA1c-1. Results: eHbA1c-1 (%) = GA × [4.688 - 18.833 × GA-1 - 0.015 × BMI - 0.037 × Hb (- 0.002 × eGFR for patients without ESRD)]-1; adjusted R 2 = 0.676 for actual HbA1c. The sensitivity of eHbA1c-1 was better than that of GA for diabetes diagnosis using the 75-g OGTT. There were no differences in the slope of eHbA1c-1 versus GA and the variance of eHbA1c-1 between the ESRD and NRF groups. eHbA1c-1 was not associated with Hb, erythropoiesis-stimulating agent use, or ESRD concomitance. Conclusions: eHbA1c-1 may be a useful parameter for estimating HbA1c in T2D patients with ESRD.

DOI： 10.1007/s13340-018-0342-6

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Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression. Reviewed International journal

Katsuyuki Tanabe, Yasufumi Sato, Jun Wada

International journal of molecular sciences 19 ( 7 ) 1859 2018.6

Language：English Publishing type：Research paper (scientific journal)

Chronic kidney disease (CKD) is a major global health problem. Unless intensive intervention is initiated, some patients can rapidly progress to end-stage kidney disease. However, it is often difficult to predict renal outcomes using conventional laboratory tests in individuals with CKD. Therefore, many researchers have been searching for novel biomarkers to predict the progression of CKD. Angiogenesis is involved in physiological and pathological processes in the kidney and is regulated by the balance between a proangiogenic factor, vascular endothelial growth factor (VEGF)-A, and various endogenous antiangiogenic factors. In recent reports using genetically engineered mice, the roles of these antiangiogenic factors in the pathogenesis of kidney disease have become increasingly clear. In addition, recent clinical studies have demonstrated associations between circulating levels of antiangiogenic factors and renal dysfunction in CKD patients. In this review, we summarize recent advances in the study of representative endogenous antiangiogenic factors, including soluble fms-related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor, VEGF-A165b, endostatin, and vasohibin-1, in associations with kidney diseases and discuss their predictive potentials as biomarkers of progression of CKD.

DOI： 10.3390/ijms19071859

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Rationale and study design of a clinical trial to assess the effects of LDL apheresis on proteinuria in diabetic patients with severe proteinuria and dyslipidemia Reviewed

Takashi Wada, Eri Muso, Shoichi Maruyama, Akinori Hara, Kengo Furuichi, Kenichi Yoshimura, Mariko Miyazaki, Eiichi Sato, Masanori Abe, Yugo Shibagaki, Ichiei Narita, Hitoshi Yokoyama, Noriko Mori, Yukio Yuzawa, Takeshi Matsubara, Tatsuo Tsukamoto, Jun Wada, Takafumi Ito, Kosuke Masutani, Kazuhiko Tsuruya, Shoichi Fujimoto, Akihiro Tsuda, Hitoshi Suzuki, Kenji Kasuno, Yoshio Terada, Takeshi Nakata, Noriaki Iino, Shuzo Kobayashi

Clinical and Experimental Nephrology 22 ( 3 ) 591 - 596 2018.6

IgA Nephropathy Complicated with X-linked Thrombocytopenia. Reviewed

Yuki Kakio, Haruhito Adam Uchida, Masashi Kitagawa, Yuka Arata, Ayako Kato, Akiko Inoue-Torii, Norikazu Hinamoto, Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Jun Wada

Acta medica Okayama 72 ( 3 ) 301 - 307 2018.6

Language：English

Renal involvement is occasionally observed in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). It has been reported that galactose-deficient IgA is a closely linked to IgA nephropathy (IgAN), suggesting that patients with XLT/WAS associated with reduced galactosylation on serum IgA are susceptible to IgAN. It is necessary to pay more attention to patients with IgAN due to the potential complication with XLT/WAS. We here present a patient of XLT complicated with mild IgAN who underwent tonsillectomy combined with steroid pulse therapy to achieve complete clinical remission.

DOI： 10.18926/AMO/56077

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Keigo Tsushida, Katsuyuki Tanabe, Kana Masuda, Satoshi Tanimura, Hiromasa Miyake, Yuka Arata, Hitoshi Sugiyama, Jun Wada

Biochemical and biophysical research communications 498 ( 4 ) 918 - 924 2018.4

Incretins modulate progesterone biosynthesis by regulating bone morphogenetic protein activity in rat granulosa cells Reviewed

Yuki Nishiyama, Toru Hasegawa, Shiho Fujita, Nahoko Iwata, Satoko Nagao, Takeshi Hosoya, Kenichi Inagaki, Jun Wada, Fumio Otsuka

Journal of Steroid Biochemistry and Molecular Biology 178 82 - 88 2018.4

Cilostazol Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysms but Not Atherosclerosis in Apolipoprotein E-Deficient Mice. Reviewed International journal

Ryoko Umebayashi, Haruhito A Uchida, Yuki Kakio, Venkateswaran Subramanian, Alan Daugherty, Jun Wada

Arteriosclerosis, thrombosis, and vascular biology 38 ( 4 ) 903 - 912 2018.4

The Prevalence of Frailty and its Associated Factors in Japanese Hemodialysis Patients. Reviewed International journal

Hidemi Takeuchi, Haruhito A Uchida, Yuki Kakio, Yuka Okuyama, Michihiro Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Jun Wada

Aging and disease 9 ( 2 ) 192 - 207 2018.4

Language：English Publishing type：Research paper (scientific journal)

The population undergoing dialysis is aging worldwide, particularly in Japan. The clinical condition of frailty is the most problematic expression in the elderly population. Potential pathophysiological factors of frailty present in patients with CKD and are accentuated in patients with ESRD. The aim of this study was to identify the prevalence and predictors of frailty in Japanese HD patients. This study was a multicenter, cross-sectional and observational investigation conducted at 6 institutions. To evaluate frailty, the modified Fried's frailty phenotype adjusted for Japanese as the self-reported questionnaire was used. Of the 542 patients visiting each institution, 388 were enrolled in this study. In total, 26.0% of participants were categorized as not-frailty, 52.6% as pre-frailty and 21.4% as frailty. The prevalence of frailty increased steadily with age and was more prevalent in females than in males and the subjects with frailty received polypharmacy. A multivariate logistic regression analysis revealed that the factors independently associated with frailty were the following: female gender (odds ratio [OR] = 3.661, 95% confidence interval [CI] 1.398-9.588), age (OR = 1.065, 95% CI 1.014-1.119), age ≥ 75 years old (OR = 4.892, 95% CI 1.715-13.955), body mass index (BMI) < 18.5 (OR = 0.110, 95% CI 0.0293-0.416), number of medications being taken (OR = 1.351, 95% CI 1.163-1.570), diabetes mellitus (DM) (OR = 2.765, 95% CI 1.081-7.071) and MNA-SF ≤ 11 (OR = 7.405, 95% CI 2.732-20.072). Frailty was associated with the accumulation of risk factors. The prevalence of frailty in Japanese patients with HD was relatively lower than that previously reported in Western developed countries; however, it was extremely high compared to the general population regardless of age. Our findings suggest that frailty might be associated with an increase in the prevalence of adverse health outcomes in patients with HD.

DOI： 10.14336/AD.2017.0429

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Other Link： http://orcid.org/0000-0001-6508-4338

The KCNQ1 gene polymorphism as a shared genetic risk for rheumatoid arthritis and chronic periodontitis in Japanese adults: A pilot case-control study. Reviewed International journal

Tetsuo Kobayashi, Jun-Ichi Kido, Yuichi Ishihara, Kazuhiro Omori, Satoshi Ito, Takato Matsuura, Takashi Bando, Jun Wada, Akira Murasawa, Kiyoshi Nakazono, Akio Mitani, Shogo Takashiba, Toshihiko Nagata, Hiromasa Yoshie

Journal of periodontology 89 ( 3 ) 315 - 324 2018.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A number of studies have suggested a bidirectional relationship of periodontitis with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). However, the genetic factors that underlie these relationships have not been elucidated. METHODS: We conducted a multicenter case-control study that included 185 patients with RA and chronic periodontitis (CP), 149 patients with T2DM and CP, 251 patients with CP, and 130 systemically and periodontally healthy controls from a cohort of Japanese adults to assess the shared genetic risk factors for RA and CP as well as for T2DM and CP. A total of 17 candidate single nucleotide polymorphisms (SNPs) associated with RA, T2DM, and CP were genotyped. RESULTS: Multiple logistic regression analyses revealed that the KCNQ1 rs2237892 was significantly associated with comorbidity of RA and CP (P = 0.005) after adjustment for age, sex, and smoking status. The carriers of the T allele among patients with RA and CP showed significantly higher disease activity scores including 28 joints using C-reactive protein values than the non-carriers (P = 0.02), although the age, female percentage, and smoking status were comparable. Other SNPs were not associated with comorbidity of RA and CP, T2DM and CP, or susceptibility to CP. CONCLUSION: The results of the present pilot study suggest for the first time that the KCNQ1 rs2237892 may constitute a shared genetic risk factor for RA and CP, but not for T2DM and CP in Japanese adults.

DOI： 10.1002/JPER.17-0412

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High calcium enhances the expression of double-stranded RNA sensors and antiviral activity in epidermal keratinocytes Reviewed

Yuriko Yamamura, Shin Morizane, Takenobu Yamamoto, Jun Wada, Keiji Iwatsuki

Experimental Dermatology 27 ( 2 ) 129 - 134 2018.2

Anti-SS-A/Ro antibody positivity as a risk factor for relapse in patients with polymyositis/dermatomyositis. Reviewed International journal

Noriko Tatebe, Ken-Ei Sada, Yosuke Asano, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Mariko Narazaki, Katsue Watanabe, Tomoko Kawabata, Jun Wada

Modern rheumatology 28 ( 1 ) 141 - 146 2018.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The objective of this study is to elucidate predictors of relapse in patients with polymyositis and dermatomyositis (PM/DM). METHODS: Fifty PM/DM patients who achieved disease stabilization at Okayama University Hospital in 2004-2014 were enrolled retrospectively. Candidate predictors such as demographic factors, clinical symptoms, laboratory data, and treatment status were compared. RESULTS: The mean age of enrolled patients was 58 years; 34 were female. The patient groupings were as follows: 21 with PM, 27 with DM, and two with clinically amyopathic DM. During a mean observation period of 685 d, 5 patients (10%) died and 20 (40%) relapsed. The relapsed patients displayed baseline muscle weakness less frequently (85% versus 100%, p = .03) and anti-SS-A/Ro antibody more frequently (65% versus 27%, p = .007). Anti-SS-A/Ro-positive patients exhibited a higher relapse rate than anti-SS-A/Ro-negative patients (log-rank test, p = .03). Anti-SS-A/Ro-positive patients also exhibited higher anti-Jo-1 antibody positivity and lower levels of serum complement. After adjusting anti-Jo-1 antibody positivity, age, sex, CK <500 IU/L, and lung involvement, anti-SS-A/Ro positivity was still an independent risk factor for higher relapse-rate (odds ratio, 5.5; 95% confidence interval, 1.4-25.1). CONCLUSIONS: Anti-SS-A/Ro antibody positivity may be a useful biomarker for prediction of relapse.

DOI： 10.1080/14397595.2017.1317377

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Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease. Reviewed International journal

Ayu Ogawa-Akiyama, Hitoshi Sugiyama, Masashi Kitagawa, Keiko Tanaka, Akifumi Onishi, Toshio Yamanari, Hiroshi Morinaga, Haruhito Adam Uchida, Kazufumi Nakamura, Hiroshi Ito, Jun Wada

PloS one 13 ( 3 ) e0193695 2018

Impact of nocturnal blood pressure variability on renal arterioles Reviewed International journal

Uchida H. A, Kitagawa M, Wada J

Hypertens Res 41 ( 1 ) 6 - 7 2018

Deletion of pro-angiogenic factor vasohibin-2 ameliorates glomerular alterations in a mouse diabetic nephropathy model. Reviewed International journal

Kana Masuda, Katsuyuki Tanabe, Haruyo Ujike, Norikazu Hinamoto, Hiromasa Miyake, Satoshi Tanimura, Hitoshi Sugiyama, Yasufumi Sato, Yohei Maeshima, Jun Wada

PloS one 13 ( 4 ) e0195779 2018

Language：English Publishing type：Research paper (scientific journal)

Angiogenesis has been implicated in glomerular alterations in the early stage of diabetic nephropathy. We previously reported the renoprotective effects of vasohibin-1 (VASH1), which is a novel angiogenesis inhibitor derived from endothelial cells, on diabetic nephropathy progression. Vasohibin-2 (VASH2) was originally identified as a VASH1 homolog and possesses pro-angiogenic activity in contrast to VASH1. In addition, VASH2 was recently shown to promote epithelial-to-mesenchymal transition via enhanced transforming growth factor (TGF)-β signaling in cancer cells. Herein, we investigated the pathogenic roles of VASH2 in diabetic nephropathy using VAHS2-deficient mice. The type 1 diabetes model was induced by intraperitoneal injections of streptozotocin in VASH2 homozygous knockout (VASH2LacZ/LacZ) or wild-type mice. These mice were euthanized 16 weeks after inducing hyperglycemia. Increased urine albumin excretion and creatinine clearance observed in diabetic wild-type mice were significantly prevented in diabetic VASH2-deficient mice. Accordingly, diabetes-induced increase in glomerular volume and reduction in glomerular slit-diaphragm density were significantly improved in VASH2 knockout mice. Increased glomerular endothelial area was also suppressed in VASH2-deficient mice, in association with inhibition of enhanced vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), but not VEGF level. Furthermore, glomerular accumulation of mesangial matrix, including type IV collagen, and increased expression of TGF-β were improved in diabetic VASH2 knockout mice compared with diabetic wild-type mice. Based on the immunofluorescence findings, endogenous VASH2 localization in glomeruli was consistent with mesangial cells. Human mesangial cells (HMCs) were cultured under high glucose condition in in vitro experiments. Transfection of VASH2 small interfering RNA (siRNA) into the HMCs resulted in the suppression of type IV collagen production induced by high glucose compared with control siRNA. These results indicate that VASH2 may be involved in diabetes-induced glomerular alterations, particularly impaired filtration barrier and mesangial expansion. Therefore, VASH2 is likely to represent a promising therapeutic target for diabetic nephropathy.

DOI： 10.1371/journal.pone.0195779

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Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease. Reviewed International journal

Toshio Yamanari, Hitoshi Sugiyama, Keiko Tanaka, Hiroshi Morinaga, Masashi Kitagawa, Akifumi Onishi, Ayu Ogawa-Akiyama, Yuzuki Kano, Koki Mise, Yasukazu Ohmoto, Kenichi Shikata, Jun Wada

BioMed research international 2018 3024698 - 3024698 2018

Language：English Publishing type：Research paper (scientific journal)

Introduction: Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods: We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m2). Results: The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion: The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

DOI： 10.1155/2018/3024698

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Olmesartan ameliorates hepatic insufficiency and serum TGF-β1 level in hypertensive patients with non-alcoholic fatty liver disease Reviewed

Nozomu Otaka, Haruhito A. Uchida, Ryoko Umebayashi, Yasuhiro Onishi, Yuka Okuyama, Hidemi Takeuchi, Yuki Kakio, Hitoshi Sugiyama, Fumio Kondo, Kazushi Harada, Hisanao Norii, Yuko Okazaki, Taro Sugimoto, Hiroo Hashimoto, Jun Wada

Therapeutic Research 39 ( 2 ) 159 - 166 2018

Correction: Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus−Derived T Cells (Journal of Immunology (2017) 198 (4268-4276) DOI: 10.4049/jimmunol.1601705)

Katsuyama, E., Yan, M., Watanabe, K.S., Narazaki, M., Matsushima, S., Yamamura, Y., Hiramatsu, S., Ohashi, K., Watanabe, H., Katsuyama, T., Zeggar, S., Yoshida, N., Moulton, V.R., Tsokos, G.C., Sada, K.-E., Wada, J.

Journal of Immunology 201 ( 3 ) 1104 - 1104 2018

Cardiovocal syndrome (Ortner syndrome) associated with secondary pulmonary arterial hypertension in a patient with mixed connective tissue disease

Jun Wada

Modern Rheumatology Case Reports 2 ( 1 ) 2018

Secretomes from Mesenchymal Stem Cells against Acute Kidney Injury: Possible Heterogeneity

Jun Wada

Stem Cells International 2018

Perplexing role of galectin 9 in experimental lupus models: comment on the article by Zeggar et al Reply

Jun Wada

Arthritis & Rheumatology 2018

TREATMENT RESPONSE AS A PREDICTOR FOR REFRACTORY DISEASE AND/OR TRANSITION TO RHEUMATOID ARTHRITIS IN PATIENTS WITH POLYMYALGIA RHEUMATICA

Jun Wada

Annals of the Rheumatic Diseases 2018

Primary peritoneal carcinosarcoma in a dialysis patient Reviewed

Keiko Tanaka, Katsuyuki Tanabe, Naoko Nishii, Kana Masuda, Yuka Arata, Akifumi Ohnishi, Masaru Kinomura, Hitoshi Sugiyama, Jun Wada

NEPHROLOGY 22 ( 11 ) 925 - 925 2017.11

The effects of non-surgical periodontal treatment on glycemic control, oxidative stress balance and quality of life in patients with type 2 diabetes: A randomized clinical trial Reviewed

Hirofumi Mizuno, Daisuke Ekuni, Takayuki Maruyama, Kota Kataoka, Toshiki Yoneda, Daiki Fukuhara, Yoshio Sugiura, Takaaki Tomofuji, Jun Wada, Manabu Morita

PLOS ONE 12 ( 11 ) e0188171 2017.11

Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who Was Unable to Continue Anti-TNF Therapy Reviewed

Eri Katsuyama, Hiroshi Wakabayashi, Ken-ei Sada, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Mariko Narazaki, Noriko Tatebe, Katsue S. Watanabe, Tomoko Kawabata, Jun Wada

ACTA MEDICA OKAYAMA 71 ( 5 ) 445 - 448 2017.10

Immunohistochemistry of Vasohibin-2 in Human Kidney Disease: Implications in Impaired Glucose Tolerance and Reduced Renal Function Reviewed

Yuka Arata, Katsuyuki Tanabe, Norikazu Hinamoto, Hiroko Yamasaki, Hitoshi Sugiyama, Yohei Maeshima, Naoki Kanomata, Yasufumi Sato, Jun Wada

ACTA MEDICA OKAYAMA 71 ( 5 ) 369 - 380 2017.10

Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice Reviewed

Haruki Watanabe, Katsue S. Watanabe, Keyue Liu, Sumie Hiramatsu, Sonia Zeggar, Eri Katsuyama, Noriko Tatebe, Akiya Akahoshi, Fumiaki Takenaka, Takahisa Hanada, Masaru Akehi, Takanori Sasaki, Ken-ei Sada, Eiji Matsuura, Masahiro Nishibori, Jun Wada

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT 6 31 - 39 2017.9

Reprogramming of metabolism in immune-mediated cells Reviewed

Jun Wada

Diabetology International 8 ( 3 ) 244 - 247 2017.8

Paratubular basement membrane insudative lesions predict renal prognosis in patients with type 2 diabetes and biopsy-proven diabetic nephropathy Reviewed

Koki Mise, Yutaka Yamaguchi, Junichi Hoshino, Toshiharu Ueno, Akinari Sekine, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Takeshi Fujii, Shigeko Hara, Hitoshi Sugiyama, Hirofumi Makino, Jun Wada, Kenichi Ohashi, Kenmei Takaichi, Yoshifumi Ubara

PLOS ONE 12 ( 8 ) e0183190 2017.8

Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells Reviewed

Kanako Ogura-Ochi, Satoshi Fujisawa, Nahoko Iwata, Motoshi Komatsubara, Yuki Nishiyama, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Jun Wada, Fumio Otsuka

PEPTIDES 94 19 - 24 2017.8

Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells Reviewed

Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R. Moulton, George C. Tsokos, Ken-Ei Sada, Jun Wada

JOURNAL OF IMMUNOLOGY 198 ( 11 ) 4268 - 4276 2017.6

Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis Reviewed

Koki Mise, Toshiharu Ueno, Junichi Hoshino, Ryo Hazue, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Takeshi Fujii, Shigeko Hara, Jun Wada, Hirofumi Makino, Kenmei Takaichi, Kenichi Ohashi, Yoshifumi Ubara

DIABETES RESEARCH AND CLINICAL PRACTICE 127 187 - 197 2017.5

A retrospective observational study of glucocorticoid-induced diabetes mellitus with IgA nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy Reviewed

Yoshia Miyawaki, Takayuki Katsuyama, Ken-Ei Sada, Sumie Hiramatsu, Keiji Ohashi, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Tatsuyuki Inoue, Masaru Kinomura, Hitoshi Sugiyama, Jun Wada

PLOS ONE 12 ( 5 ) e0178018 2017.5

Practical efficacy of olmesartan versus azilsartan in patients with hypertension: a multicenter randomized-controlled trial (MUSCAT-4 study) Reviewed

Yuki Kakio, Haruhito A. Uchida, Ryoko Umebayashi, Hidemi Takeuchi, Yuka Okuyama, Yoshihisa Hanayama, Jun Wada

BLOOD PRESSURE MONITORING 22 ( 2 ) 59 - 67 2017.4

Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions Reviewed

Motoshi Komatsubara, Takayuki Hara, Takeshi Hosoya, Kishio Toma, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Kenichi Inagaki, Jun Wada, Fumio Otsuka

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 165 ( Pt B ) 182 - 189 2017.1

Salt and sugar: Bad company Reviewed

Jun Wada

JOURNAL OF DIABETES INVESTIGATION 8 ( 1 ) 32 - 33 2017.1

Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease Reviewed

Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuhiro Nouso, Atsuko Nakatsuka, Jun Wada, Kazuko Koike, Koji Miyahara, Hidenori Shiraha, Kazuhide Yamamoto, Hiroyuki Okada

HEPATOLOGY INTERNATIONAL 11 ( 1 ) 115 - 124 2017.1

The level of urinary semaphorin3A is associated with disease activity in patients with minimal change nephrotic syndrome. Reviewed International journal

Akiko Inoue-Torii, Shinji Kitamura, Jun Wada, Kenji Tsuji, Hirofumi Makino

International journal of nephrology and renovascular disease 10 167 - 174 2017

Language：English Publishing type：Research paper (scientific journal)

Semaphorin3A is a secreted protein known to be involved in organogenesis, immune responses and cancer. In the kidney, semaphorin3A is expressed in the glomerular podocytes, distal tubules and collecting tubules, and believed to play a role in the regulation of the kidney development and function. We examined the serum and urinary semaphorin3A levels in 72 patients with renal disease and 5 healthy volunteers. The patients had been diagnosed with thin basement membrane disease (n=4), minimal change nephrotic syndrome (MCNS; n=22), IgA nephritis (n=21), membranous nephropathy (n=16) and focal segmental glomerular sclerosis (n=9). The level of urinary semaphorin3A in MCNS patients tended to be relatively high among all disease groups. We also investigated the urinary semaphorin3A level in 7 patients with MCNS from disease onset to remission during the drug therapy. MCNS patients in pre-remission states had higher urinary semaphorin3A levels than those in post-remission states receiving immunosuppressive therapies. These results suggested that the urinary semaphorin3A level correlates with the MCNS activity. Semaphorin3A has the potential as a biomarker for MCNS to clarify the reactivity for therapy and may be useful in examining other glomerular diseases with proteinuria as well.

DOI： 10.2147/IJNRD.S132980

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Sustained Tubulointerstitial Inflammation in Kidney with Severe Leptospirosis Reviewed

Keiko Tanaka, Katsuyuki Tanabe, Naoko Nishii, Keiichi Takiue, Hitoshi Sugiyama, Jun Wada

INTERNAL MEDICINE 56 ( 10 ) 1179 - 1184 2017

The Successful Treatment of Refractory Polyarteritis Nodosa Using Infliximab Reviewed

Satoko Matsuo, Keigo Hayashi, Eisaku Morimoto, Ayako Kato, Ken-Ei Sada, Haruki Watanabe, Mariko Takano-Narazaki, Katsue Sunahori-Watanabe, Tomoko Kawabata, Jun Wada

INTERNAL MEDICINE 56 ( 11 ) 1435 - 1438 2017

Occurrence of Dermatomyositis Immediately after Mastectomy Subsequent to Severe Chemotherapeutic Drug Eruption Reviewed

Yuki Otsuka, Haruki Watanabe, Yuzuki Kano, Noriko Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Ken-ei Sada, Jun Wada

INTERNAL MEDICINE 56 ( 24 ) 3379 - 3383 2017

Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents Reviewed

Takayuki Katsuyama, Ken-Ei Sada, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Eri Katsuyama, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Kohei Miyake, Toru Kiguchi, Jun Wada

MODERN RHEUMATOLOGY 27 ( 5 ) 773 - 777 2017

Antiangiogenic Therapy for Diabetic Nephropathy Reviewed

Katsuyuki Tanabe, Yohei Maeshima, Yasufumi Sato, Jun Wada

BIOMED RESEARCH INTERNATIONAL 2017 5724069 2017

Arterial Stiffness is an Independent Risk Factor for Anemia After Percutaneous Native Kidney Biopsy Reviewed

Keiko Tanaka, Masashi Kitagawa, Akifumi Onishi, Toshio Yamanari, Ayu Ogawa-Akiyama, Koki Mise, Tatsuyuki Inoue, Hiroshi Morinaga, Haruhito A. Uchida, Hitoshi Sugiyama, Jun Wada

KIDNEY & BLOOD PRESSURE RESEARCH 42 ( 2 ) 284 - 293 2017

Azathioprine Intolerance in Japanese Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis Reviewed

Michiko Morishita, Haruki Watanabe, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano Narazaki, Noriko Toyota Tatebe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

INTERNAL MEDICINE 56 ( 13 ) 1645 - 1650 2017

Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis Reviewed

Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Ken-Ei Sada, Takayuki Katsuyama, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki, Noriko Tatebe, Katsue Watanabe, Tomoko Kawabata, Jun Wada

INTERNAL MEDICINE 56 ( 21 ) 2943 - 2948 2017

Development of intracerebral hemorrhage in the short-term clinical course of a patient with microscopic polyangiitis without neurological symptoms at diagnosis: an autopsy case. Reviewed

Yoshia Miyawaki, Takayuki Katsuyama, Ken-Ei Sada, Kohei Taniguchi, Yuki Kakio, Jun Wada

CEN case reports 5 ( 2 ) 173 - 178 2016.11

Language：English Publishing type：Research paper (scientific journal)

A 77-year-old man with high-grade fever, progressive renal dysfunction, high serum level of C-reactive protein and positive serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was diagnosed with microscopic polyangiitis with rapidly progressive glomerulonephritis, and remission induction treatment with glucocorticoids and intravenous cyclophosphamide was initiated. Although his general condition improved in a short time, intracerebral hemorrhage occurred 12 days after the initiation of treatment and emergent hematoma evacuation was performed. However, he passed away on day 14. Surprisingly, even though no clinical findings for any organs except for renal involvement was detected before his death, autopsy revealed necrotizing vasculitis affecting various systemic organs including kidney, pancreas, liver, myocardium in ventricle, adipose tissue of the left adrenal gland, small intestine, gallbladder, bronchus, prostate, testis and spleen. It is difficult to detect widespread vasculitis without clinical symptoms and signs in patients with ANCA-associated vasculitis. A whole body assessment tool is necessary to detect unexpected vital organ damage, including cerebral vessels.

DOI： 10.1007/s13730-016-0219-0

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Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm Reviewed

Hidemi Takeuchi, Michihiro Okuyama, Haruhito A. Uchida, Yuki Kakio, Ryoko Umebayashi, Yuka Okuyama, Yasuhiro Fujii, Susumu Ozawa, Masashi Yoshida, Yu Oshima, Shunji Sano, Jun Wada

PLOS ONE 11 ( 10 ) e0164015 2016.10

ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism Reviewed

Zhe Tian, Keishi Miyata, Tsuyoshi Kadomatsu, Haruki Horiguchi, Hiroyuki Fukushima, Shugo Tohyama, Yoshihiro Ujihara, Takahiro Okumura, Satoshi Yamaguchi, Jiabin Zhao, Motoyoshi Endo, Jun Morinaga, Michio Sato, Taichi Sugizaki, Shunshun Zhu, Kazutoyo Terada, Hisashi Sakaguchi, Yoshihiro Komohara, Motohiro Takeya, Naoki Takeda, Kimi Araki, Ichiro Manabe, Keiichi Fukuda, Kinya Otsu, Jun Wada, Toyoaki Murohara, Satoshi Mohri, Jun K. Yamashita, Motoaki Sano, Yuichi Oike

NATURE COMMUNICATIONS 7 13016 2016.9

The possible involvement of intestine-derived IgA(1): a case of IgA nephropathy associated with Crohn's disease Reviewed

Tomohiro Terasaka, Haruhito A. Uchida, Ryoko Umebayashi, Keiko Tsukamoto, Keiko Tanaka, Masashi Kitagawa, Hitoshi Sugiyama, Hiroaki Tanioka, Jun Wada

BMC NEPHROLOGY 17 ( 1 ) 122 2016.9

Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice Reviewed

Takashi Hatanaka, Daisuke Ogawa, Hiromi Tachibana, Jun Eguchi, Tatsuyuki Inoue, Hiroshi Yamada, Kohji Takei, Hirofumi Makino, Jun Wada

Pharmacology Research and Perspectives 4 ( 4 ) e00239 2016.8

Study about the Efficacy of Metformin to Immune Function in Cancer Patients Reviewed

Mototsugu Watanabe, Hiromasa Yamamoto, Shingo Eikawa, Kazuhiko Shien, Tadahiko Shien, Junichi Soh, Katsuyuki Hotta, Jun Wada, Shiro Hinotsu, Toshiyoshi Fujiwara, Katsuyuki Kiura, Hiroyoshi Doihara, Shinichiro Miyoshi, Heiichiro Udono, Shinichi Toyooka

ACTA MEDICA OKAYAMA 70 ( 4 ) 327 - 330 2016.8

The Efficacy of Rituximab in High-risk Renal Transplant Recipients Reviewed

Motoo Araki, Koichiro Wada, Yosuke Mitsui, Risa Kubota, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 4 ) 295 - 297 2016.8

Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes Reviewed

Jun Wada, Atsuko Nakatsuka

ACTA MEDICA OKAYAMA 70 ( 3 ) 151 - 158 2016.6

Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes Reviewed

Kazutoshi Murakami, Jun Eguchi, Kazuyuki Hida, Atsuko Nakatsuka, Akihiro Katayama, Miwa Sakurai, Haruki Choshi, Masumi Furutani, Daisuke Ogawa, Kohji Takei, Fumio Otsuka, Jun Wada

DIABETES 65 ( 5 ) 1255 - 1267 2016.5

Acute idiopathic blue fingers: A young man with Achenbach's syndrome Reviewed

Hidemi Takeuchi, Haruhito Adam Uchida, Yuka Okuyama, Jun Wada

BMJ Case Reports 2016 10.1136/bcr - 2016 2016.4

Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis Reviewed

Atsuko Nakatsuka, Makoto Matsuyama, Satoshi Yamaguchi, Akihiro Katayama, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Daisuke Ogawa, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Eijiro Watanabe, Jun Wada

SCIENTIFIC REPORTS 6 21721 2016.2

The efficacy of add-on tacrolimus for minor flare in patients with systemic lupus erythematosus: a retrospective study Reviewed

H. Watanabe, R. Yamanaka, K-E Sada, S. Zeggar, E. Katsuyama, T. Katsuyama, M. T. Narazaki, N. T. Tatebe, K. Sugiyama, K. S. Watanabe, H. Wakabayashi, T. Kawabata, J. Wada, H. Makino

LUPUS 25 ( 1 ) 54 - 60 2016.1

Innate immunity in diabetes and diabetic nephropathy Reviewed

Jun Wada, Hirofumi Makino

NATURE REVIEWS NEPHROLOGY 12 ( 1 ) 13 - 26 2016.1

Risk Factors for the Requirement of Antenatal Insulin Treatment in Gestational Diabetes Mellitus Reviewed

Mayu Watanabe, Akihiro Katayama, Hidetoshi Kagawa, Daisuke Ogawa, Jun Wada

Journal of Diabetes Research 2016 9648798 2016

Bilateral Abducens Nerve Palsy due to Idiopathic Intracranial Hypertension as an Initial Manifestation of Systemic Lupus Erythematosus Reviewed

Eri Katsuyama, Ken-ei Sada, Noriko Tatebe, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Koichi Sugiyama, Katsue S. Watanabe, Hiroshi Wakabayashi, Tomoko Kawabata, Jun Wada, Hirofumi Makino

INTERNAL MEDICINE 55 ( 8 ) 991 - 994 2016

CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass Reviewed

Kitamoto, Aya, Kitamoto, Takuya, Nakamura, Takahiro, Matsuo, Tomoaki, Nakata, Yoshio, Hyogo, Hideyuki, Ochi, Hidenori, Kamohara, Seika, Miyatake, Nobuyuki, Kotani, Kazuaki, Mineo, Ikuo, Wada, Jun, Ogawa, Yuji, Yoneda, Masato, Nakajima, Atsushi, Funahashi, Tohru, Miyazaki, Shigeru, Tokunaga, Katsuto, Masuzaki, Hiroaki, Ueno, Takato, Chayama, Kazuaki, Hamaguchi, Kazuyuki, Yamada, Kentaro, Hanafusa, Toshiaki, Oikawa, Shinichi, Sakata, Toshiie, Tanaka, Kiyoji, Matsuzawa, Yuji, Hotta, Kikuko

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 23 ( 3 ) 309 - 319 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN ATHEROSCLEROSIS SOC

Aim: Visceral fat accumulation contributes to the development of metabolic syndrome. As visceral fat accumulation increases, adiponectin levels decrease; therefore, adiponectin provides a link between visceral fat accumulation and metabolic disorders. Genome-wide association studies (GWASs) have identified genetic variations in the cadherin 13 (CDH13) gene that are associated with adiponectin levels. Methods: We investigated whether single nucleotide polymorphisms (SNPs) in CDH13 was associated with adiponectin levels and metabolic syndrome traits independent of the visceral fat area (VFA), as measured using computed tomography (CT) in 945 Japanese individuals. Results: We found that three CDH13 SNPs reported by recent GWASs (i.e., rs3865188, rs4783244, and rs12051272) were significantly associated with higher adiponectin levels (P < 1 x 10(-14)), even after adjustment for VFA. However, these adiponectin-inducing alleles of CDH13 SNPs were significantly associated with traits consistent with deteriorating metabolic symptoms, such as higher fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) scores, and triglycerides and lower highdensity lipoprotein (HDL)-cho

DOI： 10.5551/jat.31567

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Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial Reviewed

Sawako Kato, Shoichi Maruyama, Hirofumi Makino, Jun Wada, Daisuke Ogawa, Takashi Uzu, Hisazumi Araki, Daisuke Koya, Keizo Kanasaki, Yutaka Oiso, Motomitsu Goto, Akira Nishiyama, Hiroyuki Kobori, Enyu Imai, Masahiko Ando, Seiichi Matsuo

CLINICAL AND EXPERIMENTAL NEPHROLOGY 19 ( 6 ) 1098 - 1106 2015.12

Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis Reviewed

Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Kazutoshi Murakami, Sanae Teshigawara, Motoko Kanzaki, Tomokazu Nunoue, Kazuyuki Hida, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Akinobu Takaki, Kazuhide Yamamoto, Hiroshi Kiyonari, Hirofumi Makino, Jun Wada

SCIENTIFIC REPORTS 5 16920 2015.11

Successful treatment by mycophenolate mofetil in a patient with focal segmental glomerulosclerosis associated with posterior reversible encephalopathy syndrome. Reviewed

Tenta M, Uchida HA, Nunoue T, Umebayashi R, Okuyama Y, Kitagawa M, Maeshima Y, Sugiyama H, Wada J

CEN case reports 4 ( 2 ) 190 - 195 2015.11

Language：English Publishing type：Research paper (scientific journal)

It has been reported that cyclosporine A (CsA) treatment may be associated with posterior reversible encephalopathy syndrome. We report a 16-year-old man who exhibited nephrotic syndrome and posterior reversible encephalopathy syndrome. Intensive antihypertensive therapy restored him to consciousness. Renal biopsy revealed that he suffered from focal segmental glomerulosclerosis. Although he was treated with prednisolone and low-density lipoprotein apheresis therapy, his proteinuria remained at high level. Then, mycophenolate mofetil (MMF) with less influence on vessel endothelium compared with CsA and tacrolimus was administered. Soon after, he reached remission of nephrotic syndrome without recurrence of posterior reversible encephalopathy syndrome. This is the first case that a young patient of focal segmental glomerulosclerosis with posterior reversible encephalopathy syndrome achieved a complete remission by MMF treatment without recurrence of posterior reversible encephalopathy syndrome. MMF may be effective for young patients of focal segmental glomerulosclerosis especially with clinical condition of vascular endothelial damage such as posterior reversible encephalopathy syndrome.

DOI： 10.1007/s13730-014-0165-7

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Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes Reviewed

Yu Wang, Akihiro Katayama, Takahiro Terami, Xiaoying Han, Tomokazu Nunoue, Dongxiao Zhang, Sanae Teshigawara, Jun Eguchi, Atsuko Nakatsuka, Kazutoshi Murakami, Daisuke Ogawa, Yasuhide Furuta, Hirofumi Makino, Jun Wada

METABOLISM-CLINICAL AND EXPERIMENTAL 64 ( 6 ) 677 - 688 2015.6

Risk factors for the development of glucocorticoid-induced diabetes mellitus Reviewed

Takayuki Katsuyama, Ken-Ei Sada, Sayaka Namba, Haruki Watanabe, Eri Katsuyama, Toshio Yamanari, Jun Wada, Hirofumi Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 108 ( 2 ) 273 - 279 2015.5

Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes Reviewed

Chigusa Higuchi, Atsuko Nakatsuka, Jun Eguchi, Sanae Teshigawara, Motoko Kanzaki, Akihiro Katayama, Satoshi Yamaguchi, Naoto Takahashi, Kazutoshi Murakami, Daisuke Ogawa, Sakiko Sasaki, Hirofumi Makino, Jun Wada

METABOLISM-CLINICAL AND EXPERIMENTAL 64 ( 4 ) 489 - 497 2015.4

AUTOIMMUNE PANCREATITIS AND MINIMAL CHANGE NEPHROTIC SYNDROME: AN UNUSUAL ASSOCIATION? Reviewed

Yuka Okuyama, Haruhito Adam Uchida, Masafumi Tenta, Tomokazu Nunoue, Ryoko Umebayashi, Hiroshi Morinaga, Shinji Kitamura, Yohei Maeshima, Hitoshi Sugiyama, Jun Wada

NEPHROLOGY 20 ( 3 ) 225 - 226 2015.3

Cognitive and affective functions in diabetic patients associated with diabetes-related factors, white matter abnormality and aging Reviewed

N. Hishikawa, T. Yamashita, K. Deguchi, J. Wada, K. Shikata, H. Makino, K. Abe

EUROPEAN JOURNAL OF NEUROLOGY 22 ( 2 ) 313 - 321 2015.2

Structural design and synthesis of arylalkynyl amide-type peroxisome proliferator-activated receptor gamma (PPAR gamma)-selective antagonists based on the helix12-folding inhibition hypothesis Reviewed

Masao Ohashi, Kanae Gamo, Yuta Tanaka, Minoru Waki, Yoko Beniyama, Kenji Matsuno, Jun Wada, Masafumi Tenta, Jun Eguchi, Makoto Makishima, Nobuyasu Matsuura, Takuji Oyama, Hiroyuki Miyachi

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 90 53 - 67 2015.1

ADIPOQ polymorphisms are associated with insulin resistance in Japanese women

Kitamoto, Aya, Kitamoto, Takuya, So, Rina, Matsuo, Tomoaki, Nakata, Yoshio, Hyogo, Hideyuki, Ochi, Hidenori, Nakamura, Takahiro, Kamohara, Seika, Miyatake, Nobuyuki, Kotani, Kazuaki, Mineo, Ikuo, Wada, Jun, Ogawa, Yuji, Yoneda, Masato, Nakajima, Atsushi, Funahashi, Tohru, Miyazaki, Shigeru, Tokunaga, Katsuto, Masuzaki, Hiroaki, Ueno, Takato, Chayama, Kazuaki, Hamaguchi, Kazayuki, Yamada, Kentaro, Hanafusa, Toshiaki, Oikawa, Shinichi, Sakata, Toshiie, Tanaka, Kiyoji, Matsuzawa, Yuji, Hotta, Kikuko

ENDOCRINE JOURNAL 62 ( 6 ) 513 - 521 2015

Language：English Publishing type：Research paper (scientific journal)

Visceral fat accumulation contributes to the development of insulin resistance, leading to metabolic syndrome. Adiponectin provides a link between visceral fat accumulation and insulin resistance. In addition to environmental factors, genetic factors play important roles in visceral fat accumulation and circulating adiponectin levels. Genome-wide association studies (GWASs) have identified genetic variations in the adiponectin, C1Q and collagen domain containing (ADIPOQ) gene that are associated with adiponectin levels. In this study, we investigated whether ADIPOQ single nucleotide polymorphisms (SNPs) were associated with visceral fat accumulation and insulin resistance. We measured the visceral fat area (VFA) by computed tomography (CT) and examined the presence of the insulin resistance-related phenotype (fasting plasma glucose, fasting insulin, and homeostasis model assessment-insulin resistance [HOMA-IR]) in a set of Japanese individuals (731 men and 864 women) who were genotyped for seven ADIPOQ SNPs reported by recent GWASs (namely, rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957). SNPs associated with the phenotype (P < 0.05) were then evaluated by association analysis using a second set of the study participants (383 men and 510 women). None of the SNPs was associated with body mass index (BMI) or VFA in men or women. However, the adiponectin-decreasing alleles of rs10937273 and rs1648707 were significantly associated with HOMA-IR (P = 0.0030 and P = 0.00074, respectively) in women, independently of BMI. These SNPs were significantly associated with decreased adiponectin levels in women. Our results suggested that rs10937273 and rs1648707 may affect insulin sensitivity by regulating adiponectin production by adipose tissue in women.

DOI： 10.1507/endocrj.EJ14-0574

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Factors Associated with Remission and/or Regression of Microalbuminuria in Type 2 Diabetes Mellitus Reviewed

Tetsuichiro Ono, Kenichi Shikata, Mikako Obika, Nobuyuki Miyatake, Ryo Kodera, Daisyo Hirota, Jun Wada, Hitomi Kataoka, Daisuke Ogawa, Hirofumi Makino

ACTA MEDICA OKAYAMA 68 ( 4 ) 235 - 241 2014.8

Long-Term Treatment with the Sodium Glucose Cotransporter 2 Inhibitor, Dapagliflozin, Ameliorates Glucose Homeostasis and Diabetic Nephropathy in db/db Mice Reviewed

Naoto Terami, Daisuke Ogawa, Hiromi Tachibana, Takashi Hatanaka, Jun Wada, Atsuko Nakatsuka, Jun Eguchi, Chikage Sato Horiguchi, Naoko Nishii, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

PLOS ONE 9 ( 6 ) e100777 2014.6

Serum vaspin levels are associated with physical activity or physical fitness in Japanese: a pilot study

Nobuyuki Miyatake, Jun Wada, Atsuko Nakatsuka, Noriko Sakano, Sanae Teshigawara, Motohiko Miyachi, Izumi Tabata, Takeyuki Numata

ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 19 ( 3 ) 200 - 206 2014.5

Pemt Deficiency Ameliorates Endoplasmic Reticulum Stress in Diabetic Nephropathy Reviewed

Mayu Watanabe, Atsuko Nakatsuka, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Chigusa Higuchi, Akihiro Katayama, Sanae Teshigawara, Jun Eguchi, Daisuke Ogawa, Eijiro Watanabe, Jun Wada, Hirofumi Makino

PLOS ONE 9 ( 3 ) e92647 2014.3

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats Reviewed

Toru Miyoshi, Kazufumi Nakamura, Masashi Yoshida, Daiji Miura, Hiroki Oe, Satoshi Akagi, Hiroki Sugiyama, Kaoru Akazawa, Tomoko Yonezawa, Jun Wada, Hiroshi Ito

CARDIOVASCULAR DIABETOLOGY 13 43 2014.2

Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice Reviewed

Hiromi Tachibana, Daisuke Ogawa, Norio Sogawa, Masato Asanuma, Ikuko Miyazaki, Naoto Terami, Takashi Hatanaka, Chikage Sato Horiguchi, Atsuko Nakatsuka, Jun Eguchi, Jun Wada, Hiroshi Yamada, Kohji Takei, Hirofumi Makino

American Journal of Physiology - Renal Physiology 306 ( 1 ) F105 - F115 2014.1

Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice Reviewed

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 306 ( 1 ) F105 - F115 2014.1

Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines Reviewed

Daisuke Ogawa, Jun Eguchi, Jun Wada, Naoto Terami, Takashi Hatanaka, Hiromi Tachibana, Atsuko Nakatsuka, Chikage Sato Horiguchi, Naoko Nishii, Hirofumi Makino

PLOS ONE 9 ( 1 ) e85594 2014.1

Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl peptidase-4 inhibitor Reviewed

Ken-Ei Sada, Jun Wada, Hiroshi Morinaga, Shigeyuki Tuchimochi, Mayu Uka, Hirofumi Makino

Clinical Kidney Journal 7 ( 2 ) 182 - 185 2014

The chemiexcitation of the chemiluminescence of lophine peroxide anions via a partially cyclic transition state

Lu, G., Wada, J., Kimoto, T., Iga, H., Nishigawa, H., Kimura, M., Hu, Z.

European Journal of Organic Chemistry 2014 ( 6 ) 2014

Comparison of New Preservation Solutions, HN-1 and University of Wisconsin Solution, in Pancreas Preservation for Porcine Islet Isolation. Reviewed

Katayama A, Noguchi H, Kuise T, Nakatsuka A, Hirota D, Kataoka HU, Kawai T, Inoue K, Imagawa N, Saitoh I, Noguchi Y, Watanabe M, Wada J, Fujiwara T

Cell medicine 6 ( 1-2 ) 3 - 8 2013.12

Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism Reviewed

Kazunori Nakayama, Kazushi Nakao, Yuji Takatori, Junko Inoue, Shoichirou Kojo, Shigeru Akagi, Masaki Fukushima, Jun Wada, Hirofumi Makino

International Journal of Nephrology and Renovascular Disease 7 25 - 33 2013.12

Urinary angiotensinogen is a marker for tubular injuries in patients with type 2 diabetes Reviewed

Takahiro Terami, Jun Wada, Kentaro Inoue, Atsuko Nakatsuka, Daisuke Ogawa, Sanae Teshigawara, Kazutoshi Murakami, Akihiro Katayama, Jun Eguchi, Hirofumi Makino

International Journal of Nephrology and Renovascular Disease 6 233 - 240 2013.10

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray Reviewed

Kentaro Inoue, Jun Wada, Jun Eguchi, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Daisuke Ogawa, Takahiro Terami, Akihiro Katayama, Atsuhito Tone, Izumi Iseda, Kazuyuki Hida, Masao Yamada, Tomohisa Ogawa, Hirofumi Makino

PLoS ONE 8 ( 10 ) e77118 2013.10

NUDT3 rs206936 is associated with body mass index in obese Japanese women Reviewed

Kitamoto, A., Kitamoto, T., Mizusawa, S., Teranishi, H., So, R., Matsuo, T., Nakata, Y., Hyogo, H., Ochi, H., Nakamura, T., Kamohara, S., Miyatake, N., Kotani, K., Komatsu, R., Itoh, N., Mineo, I., Wada, J., Yoneda, M., Nakajima, A., Funahashi, T., Miyazaki, S., Tokunaga, K., Masuzaki, H., Ueno, T., Chayama, K., Hamaguchi, K., Yamada, K., Hanafusa, T., Oikawa, S., Sakata, T., Tanaka, K., Matsuzawa, Y., Nakao, K., Sekine, A., Hotta, K.

Endocrine Journal 60 ( 8 ) 991 - 1000 2013.8

Cell Cycle Abnormality in Metabolic Syndrome and Nuclear Receptors as an Emerging Therapeutic Target Reviewed

Atsuko Nakatsuka, Jun Wada, Hirofumi Makino

ACTA MEDICA OKAYAMA 67 ( 3 ) 129 - 134 2013.6

Visceral Adipose Tissue-derived Serine Proteinase Inhibitor Inhibits Apoptosis of Endothelial Cells as a Ligand for the Cell-Surface GRP78/Voltage-dependent Anion Channel Complex Reviewed

Atsuko Nakatsuka, Jun Wada, Izumi Iseda, Sanae Teshigawara, Kanji Higashio, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Kazuyuki Hida, Jun Eguchi, Daisuke Ogawa, Yasushi Matsuki, Ryuji Hiramatsu, Hideo Yagita, Shigeru Kakuta, Yoichiro Iwakura, Hirofumi Makino

CIRCULATION RESEARCH 112 ( 5 ) 771 - + 2013.3

Current status of the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in Japan Reviewed

Koichi Sugiyama, Ken-Ei Sada, Michiko Kurosawa, Jun Wada, Hirofumi Makino

Clinical and Experimental Nephrology 17 ( 1 ) 51 - 58 2013.2

Inflammation and the pathogenesis of diabetic nephropathy Reviewed

Jun Wada, Hirofumi Makino

CLINICAL SCIENCE 124 ( 3-4 ) 139 - 152 2013.2

The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO) Reviewed

Kazutoshi Murakami, Jun Wada, Daisuke Ogawa, Chikage Sato Horiguchi, Tomoko Miyoshi, Motofumi Sasaki, Haruhito A. Uchida, Yoshio Nakamura, Hirofumi Makino

DIABETES & VASCULAR DISEASE RESEARCH 10 ( 1 ) 93 - 96 2013.1

Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease Reviewed

Yuko Kurose, Jun Wada, Motoko Kanzaki, Sanae Teshigawara, Atsuko Nakatsuka, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Mayu Watanabe, Chigusa Higuchi, Jun Eguchi, Nobuyuki Miyatake, Hirofumi Makino

BMC NEPHROLOGY 14 2013.1

Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population Reviewed

Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Rina So, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 20 ( 4 ) 336 - 350 2013

The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO) (vol 10, pg 93, 2013)

Jun Wada

Diabetes and Vascular Disease Research 10 ( 6 ) 554 - 554 2013

Erratum: Telmisartan attenutes diabetic nephropathy by suppressing oxisative stress in db/db mice (Nephron - Experimental Nephrology (2012) 121 (e97-e108) DOI: 10.1159/00343102)

Sato-Horiguchi, C., Ogawa, D., Wada, J., Tachibana, H., Kodera, R., Eguchi, J., Nakatsuka, A., Terami, N., Shikata, K., Makino, H.

Nephron - Experimental Nephrology 123 ( 3-4 ) 46 - 46 2013

Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines

Jun Wada

Diabetes 2013

The serum vaspin levels are reduced in Japanese chronic hemodialysis patients Reviewed

Junko Inoue, Jun Wada, Sanae Teshigawara, Kazuyuki Hida, Atsuko Nakatsuka, Yuji Takatori, Shoichirou Kojo, Shigeru Akagi, Kazushi Nakao, Nobuyuki Miyatake, John F. McDonald, Hirofumi Makino

BMC NEPHROLOGY 13 2012.12

Case of emphysematous cholecystitis in a patient with type 2 diabetes mellitus associated with schizophrenia Reviewed

Ayu Ogawa, Kenichi Shikata, Haruhito Adam Uchida, Susumu Shinoura, Naosuke Yokomichi, Daisuke Ogawa, Chicage Sato-Horiguchi, Takahito Yagi, Jun Wada, Hirofumi Makino

JOURNAL OF DIABETES INVESTIGATION 3 ( 6 ) 534 - 535 2012.12

Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex Reviewed

Atsuko Nakatsuka, Jun Wada, Izumi Iseda, Sanae Teshigawara, Kanji Higashio, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Kazuyuki Hida, Jun Eguchi, Chikage Sato Horiguchi, Daisuke Ogawa, Yasushi Matsuki, Ryuji Hiramatsu, Hideo Yagita, Shigeru Kakuta, Yoichiro Iwakura, Hirofumi Makino

DIABETES 61 ( 11 ) 2823 - 2832 2012.11

Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy Reviewed

Hiromi Tachibana, Daisuke Ogawa, Yuichi Matsushita, Dennis Bruemmer, Jun Wada, Sanae Teshigawara, Jun Eguchi, Chikage Sato-Horiguchi, Haruhito Adam Uchida, Kenichi Shikata, Hirofumi Makino

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 23 ( 11 ) 1835 - 1846 2012.11

Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice Reviewed

Daisuke Kawai, Akinobu Takaki, Atsuko Nakatsuka, Jun Wada, Naofumi Tamaki, Tetsuya Yasunaka, Kazuko Koike, Ryuichiro Tsuzaki, Kazuyuki Matsumoto, Yasuhiro Miyake, Hidenori Shiraha, Manabu Morita, Hirofumi Makino, Kazuhide Yamamoto

HEPATOLOGY 56 ( 3 ) 912 - 921 2012.9

Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 at SERPINA12 Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population Reviewed

Sanae Teshigawara, Jun Wada, Kazuyuki Hida, Atsuko Nakatsuka, Jun Eguchi, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Izumi Iseda, Yuichi Matsushita, Nobuyuki Miyatake, John F. McDonald, Kikuko Hotta, Hirofumi Makino

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 97 ( 7 ) E1202 - E1207 2012.7

Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography Reviewed

Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Rina So, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

JOURNAL OF HUMAN GENETICS 57 ( 5 ) 305 - 310 2012.5

RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21(Cip1) pathway in adipocytes Reviewed

Atsuko Nakatsuka, Jun Wada, Kazuyuki Hida, Aya Hida, Jun Eguchi, Sanae Teshigawara, Kazutoshi Murakami, Motoko Kanzaki, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Daisuke Ogawa, Hiroyuki Kagechika, Hirofumi Makino

JOURNAL OF PATHOLOGY 226 ( 5 ) 784 - 795 2012.4

Impact of circulating vaspin levels on metabolic variables in elderly twins Reviewed

K. Hida, P. Poulsen, S. Teshigawara, E. Nilsson, M. Friedrichsen, R. Ribel-Madsen, L. Grunnet, S. S. Lund, J. Wada, A. Vaag

DIABETOLOGIA 55 ( 2 ) 530 - 532 2012.2

Galectin-9 and T Cell Immunoglobulin Mucin-3 Pathway Is a Therapeutic Target for Type 1 Diabetes Reviewed

Motoko Kanzaki, Jun Wada, Koichi Sugiyama, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Jun Eguchi, Hisaya Akiba, Hideo Yagita, Hirofumi Makino

ENDOCRINOLOGY 153 ( 2 ) 612 - 620 2012.2

Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women Reviewed

Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

JOURNAL OF HUMAN GENETICS 57 ( 1 ) 46 - 51 2012.1

The therapeutic potential of synthetic human atrial natriuretic peptide in nephrotic syndrome: a randomized controlled trial Reviewed

Jun Wada

International Journal of Nephrology and Renovascular Disease 5 91 - 6 2012

A Case of Type 2 Diabetes and Metastatic Liver Cancer Exhibiting Hypercholesterolemia with Abnormal Lipoproteins Reviewed

Motoko Kanzaki, Jun Wada, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Akihiro Katayama, Junichiro Nasu, Kazuhide Yamamoto, Hirofumi Makino

INTERNAL MEDICINE 51 ( 6 ) 619 - 623 2012

Telmisartan Attenuates Diabetic Nephropathy by Suppressing Oxidative Stress in db/db Mice Reviewed

Chikage Sato-Horiguchi, Daisuke Ogawa, Jun Wada, Hiromi Tachibana, Ryo Kodera, Jun Eguchi, Atsuko Nakatsuka, Naoto Terami, Kenichi Shikata, Hirofumi Makino

NEPHRON EXPERIMENTAL NEPHROLOGY 121 ( 3-4 ) E97 - E108 2012

Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area Reviewed

Kikuko Hotta, Takuya Kitamoto, Aya Kitamoto, Seiho Mizusawa, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

JOURNAL OF HUMAN GENETICS 56 ( 10 ) 716 - 719 2011.10

Two novel mutations of lecithin:cholesterol acyltransferase (LCAT) gene and the influence of APOE genotypes on clinical manifestations Reviewed

Katayama, A., Wada, J., Kataoka, H.U., Yamasaki, H., Teshigawara, S., Terami, T., Inoue, K., Kanzaki, M., Murakami, K., Nakatsuka, A., Sugiyama, H., Koide, N., Bujo, H., Makino, H.

NDT Plus 4 ( 5 ) 299 - 302 2011.10

Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population Reviewed

Kikuko Hotta, Takuya Kitamoto, Aya Kitamoto, Seiho Mizusawa, Tomoaki Matsuo, Yoshio Nakata, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

JOURNAL OF HUMAN GENETICS 56 ( 9 ) 647 - 651 2011.9

Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy Reviewed

Naomi Watanabe, Kenichi Shikata, Yasushi Shikata, Kei Sarai, Kazuyoshi Omori, Ryo Kodera, Chikage Sato, Jun Wada, Hirofumi Makino

ACTA MEDICA OKAYAMA 65 ( 4 ) 247 - 257 2011.8

Icodextrin Increases Technique Survival Rate in Peritoneal Dialysis Patients with Diabetic Nephropathy by Improving Body Fluid Management: A Randomized Controlled Trial Reviewed

Yuji Takatori, Shigeru Akagi, Hitoshi Sugiyama, Junko Inoue, Shoichiro Kojo, Hiroshi Morinaga, Kazushi Nakao, Jun Wada, Hirofumi Makino

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 6 ( 6 ) 1337 - 1344 2011.6

Emphysematous Cystitis in a Patient with Type 2 Diabetes Mellitus Reviewed

Noriko Toyota, Daisuke Ogawa, Keita Ishii, Kyoji Hirata, Jun Wada, Kenichi Shikata, Hirofumi Makino

ACTA MEDICA OKAYAMA 65 ( 2 ) 129 - 133 2011.4

Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis after subtotal nephrectomy Reviewed

Yuichi Kido, Daisuke Ogawa, Kenichi Shikata, Motofumi Sasaki, Ryo Nagase, Shinichi Okada, Hitomi Usui Kataoka, Jun Wada, Hirofumi Makino

CLINICAL AND EXPERIMENTAL NEPHROLOGY 15 ( 2 ) 212 - 219 2011.4

The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration Reviewed

Motofumi Sasaki, Kenichi Shikata, Shinichi Okada, Satoshi Miyamoto, Shingo Nishishita, Hitomi Usui Kataoka, Chikage Sato, Jun Wada, Daisuke Ogawa, Hirofumi Makino

ACTA MEDICA OKAYAMA 65 ( 2 ) 81 - 89 2011.4

Activation of Peroxisome Proliferator-Activated Receptor delta Inhibits Streptozotocin-Induced Diabetic Nephropathy Through Anti-Inflammatory Mechanisms in Mice Reviewed

Yuichi Matsushita, Daisuke Ogawa, Jun Wada, Noriko Yamamoto, Kenichi Shikata, Chikage Sato, Hiromi Tachibana, Noriko Toyota, Hirofumi Makino

DIABETES 60 ( 3 ) 960 - 968 2011.3

P-Selectin Glycoprotein Ligand-1 Deficiency Is Protective Against Obesity-Related Insulin Resistance Reviewed

Chikage Sato, Kenichi Shikata, Daisho Hirota, Motofumi Sasaki, Shingo Nishishita, Satoshi Miyamoto, Ryo Kodera, Daisuke Ogawa, Atsuhito Tone, Hitomi Usui Kataoka, Jun Wada, Nobuo Kajitani, Hirofumi Makino

DIABETES 60 ( 1 ) 189 - 199 2011.1

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells Reviewed

Daisuke Ogawa, Masato Asanuma, Ikuko Miyazaki, Hiromi Tachibana, Jun Wada, Norio Sogawa, Takeshi Sugaya, Shinji Kitamura, Yohei Maeshima, Kenichi Shikata, Hirofumi Makino

EXPERIMENTAL DIABETES RESEARCH 2011

Discovery of Genes Related to Diabetic Nephropathy in Various Animal Models by Current Techniques Reviewed

Jun Wada, Lin Sun, Yashpal S. Kanwar

EXPERIMENTAL MODELS FOR RENAL DISEASES: PATHOGENESIS AND DIAGNOSIS 169 161 - 174 2011

[Obesity: Progress in diagnosis and treatment; Topics, IV. Recent topics: 3. Obesity and new secretory factors; 1) Vaspin].

Wada, J., Teshigawara, S., Nakatsuka, A., Makino, H.

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 100 ( 4 ) 2011

Regulation of human serum vaspin levels and metabolic syndrome

Wada, J.

Therapeutic Research 32 ( 6 ) 2011

[Chronic kidney disease].

Katayama, A., Wada, J., Makino, H.

Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 1 2011

[Chemerin, RBP4 and vaspin].

Wada, J., Teshigawara, S., Nakatsuka, A.

Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 1 2011

Insufficient control of morning home blood pressure in Japanese patients with hypertension associated with diabetes mellitus Reviewed

Haruhito A. Uchida, Yoshio Nakamura, Hisanao Norii, Masanobu Kaihara, Yoshihisa Hanayama, Ken-Ei Sada, Jun Wada, Kenichi Shikata, Hirofumi Makino

JOURNAL OF DIABETES INVESTIGATION 1 ( 6 ) 266 - 272 2010.12

Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population Reviewed

Kikuko Hotta, Michihiro Nakamura, Takahiro Nakamura, Tomoaki Matsuo, Yoshio Nakata, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Hiroaki Masuzaki, Takato Ueno, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Yusuke Nakamura, Naoyuki Kamatani

JOURNAL OF HUMAN GENETICS 55 ( 11 ) 738 - 742 2010.11

Peramivir for Severe Influenza Infection in a Patient with Diabetic Nephropathy Reviewed

Tatsuyo Nasu, Daisuke Ogawa, Jun Wada, Hirofumi Makino

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 182 ( 9 ) 1209 - 1210 2010.11

In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7 Reviewed

Qingxian Zhang, Yonghong Shi, Jun Wada, Sandra M. Malakauskas, Maodong Liu, Yunzhuo Ren, Chunyang Du, Huijun Duan, Yingmin Li, Ying Li, Yanling Zhang

PLOS ONE 5 ( 7 ) 2010.7

Comparison of Insulin Detemir and Insulin Glargine on Glycemic Variability in Patients with Type 1 and Type 2 Diabetes Reviewed

A. Tone, I. Iseda, C. Higuchi, K. Tsukamoto, A. Katayama, Y. Matsushita, K. Hida, J. Wada, K. Shikata

EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES 118 ( 5 ) 320 - 324 2010.5

Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy Reviewed

Ai Nakao, Kazushi Nakao, Yuji Takatori, Syoichirou Kojo, Junko Inoue, Shigeru Akagi, Hitoshi Sugiyama, Jun Wada, Hirofumi Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 25 ( 5 ) 1479 - 1488 2010.5

The Usefulness of Super-Selective Computed Tomography Angiography (CTA) for Diagnosing and Localizing a Small Insulinoma Reviewed

Akihiro Katayama, Izumi Iseda, Atsuhito Tone, Yuichi Matsushita, Kentaro Inoue, Keiko Tsukamoto, Haruhiro Yamashita, Ichiro Yamadori, Jun Wada, Kazuyuki Hida

INTERNAL MEDICINE 49 ( 18 ) 1983 - 1986 2010

Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population Reviewed

Kikuko Hotta, Michihiro Nakamura, Takahiro Nakamura, Tomoaki Matsuo, Yoshio Nakata, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Takato Ueno, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura

JOURNAL OF HUMAN GENETICS 54 ( 12 ) 727 - 731 2009.12

Endothelial barrier protection by FTY720 under hyperglycemic condition: involvement of focal adhesion kinase, small GTPases, and adherens junction proteins Reviewed

Kei Sarai, Kenichi Shikata, Yasushi Shikata, Kazuyoshi Omori, Naomi Watanabe, Motofumi Sasaki, Shingo Nishishita, Jun Wada, Noriko Goda, Noriyuki Kataoka, Hirofumi Makino

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 297 ( 4 ) C945 - C954 2009.10

Historical chronology of basic and clinical research in diabetic nephropathy and contributions of Japanese scientists Reviewed

Jun Wada, Hirofumi Makino

CLINICAL AND EXPERIMENTAL NEPHROLOGY 13 ( 5 ) 405 - 414 2009.10

Enhanced interaction between focal adhesion and adherens junction proteins: Involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement Reviewed

Xiaoguang Sun, Yasushi Shikata, Lichun Wang, Kazuyoshi Ohmori, Naoko Watanabe, Jun Wada, Kenichi Shikata, Konstantin G. Birukov, Hirofumi Makino, Jeffrey R. Jacobson, Steven M. Dudek, Joe G. N. Garcia

MICROVASCULAR RESEARCH 77 ( 3 ) 304 - 313 2009.5

Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome Reviewed

Kikuko Hotta, Takahiro Nakamura, Junichi Takasaki, Hiroshi Takahashi, Atsushi Takahashi, Yoshio Nakata, Seika Kamohara, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura

JOURNAL OF HUMAN GENETICS 54 ( 4 ) 230 - 235 2009.4

Rap1b GTPase Ameliorates Glucose-Induced Mitochondrial Dysfunction Reviewed

Lin Sun, Ping Xie, Jun Wada, Naoki Kashihara, Fu-you Liu, Yanan Zhao, Deepak Kumar, Sumant S. Chugh, Farhad R. Danesh, Yashpal S. Kanwar

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 19 ( 12 ) 2293 - 2301 2008.12

Bilateral dystonia in type 1 diabetes: A case report Reviewed

Akihiro Yasuhara, Jun Wada, Hirofumi Makino

Journal of Medical Case Reports 2 352 2008.11

Collectrin Is Involved in the Development of Salt-Sensitive Hypertension by Facilitating the Membrane Trafficking of Apical Membrane Proteins via Interaction With Soluble N-Ethylmaleiamide-Sensitive Factor Attachment Protein Receptor Complex Reviewed

Akihiro Yasuhara, Jun Wada, Sandra M. Malakauskas, Yanling Zhang, Jun Eguchi, Atsuko Nakatsuka, Kazutoshi Murakami, Motoko Kanzaki, Sanae Teshigawara, Kazuya Yamagata, Thu H. Le, Hirofumi Makino

CIRCULATION 118 ( 21 ) 2146 - 2155 2008.11

INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese Reviewed

Kikuko Hotta, Michihiro Nakamura, Yoshio Nakata, Tomoaki Matsuo, Seika Kamohara, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Tohru Funahashi, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Kiyoji Tanaka, Naoyuki Kamatani, Yusuke Nakamura

JOURNAL OF HUMAN GENETICS 53 ( 9 ) 857 - 862 2008.9

Variations in the FTO gene are associated with severe obesity in the Japanese Reviewed

Kikuko Hotta, Yoshio Nakata, Tomoaki Matsuo, Seika Kamohara, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Tohru Funahashi, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Kiyoji Tanaka, Naoyuki Kamatani, Yusuke Nakamura

JOURNAL OF HUMAN GENETICS 53 ( 6 ) 546 - 553 2008.6

Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysis Reviewed

Kousuke Fukuoka, Kazushi Nakao, Hisanori Morimoto, Ai Nakao, Yuji Takatori, Katsuhiko Arimoto, Masafumi Taki, Jun Wada, Hirofumi Makino

NEPHROLOGY 13 ( 4 ) 278 - 283 2008.6

Procollagen C-proteinase enhancer-1 (POPE-1) interacts with beta 2-microglobulin (beta 2-m) and may help initiate beta 2-m amyloid fibril formation in connective tissues Reviewed

Hisanori Morimoto, Jun Wada, Bernard Font, Joni D. Mott, David J. S. Hulmes, Tadakazu Ookoshi, Hironobu Naiki, Akihiro Yasuhara, Atsuko Nakatsuka, Kousuke Fukuoka, Yuji Takatori, Haruo Ichikawa, Shigeru Akagi, Kazushi Nakao, Hirofumi Makino

MATRIX BIOLOGY 27 ( 3 ) 211 - 219 2008.4

Vaspin: a novel serpin with insulin-sensitizing effects Reviewed

Jun Wada

EXPERT OPINION ON INVESTIGATIONAL DRUGS 17 ( 3 ) 327 - 333 2008.3

Diabetic nephropathy: Mechanisms of renal disease progression Reviewed

Yashpal S. Kanwar, Jun Wada, Lin Sun, Ping Xie, Elisabeth I. Wallner, Sheldon Chen, Sumant Chugh, Farhad R. Danesh

EXPERIMENTAL BIOLOGY AND MEDICINE 233 ( 1 ) 4 - 11 2008.1

Comparison of serum uric acid levels between Japanese with and without metabolic syndrome

Numata, T., Miyatake, N., Wada, J., Makino, H.

Diabetes Research and Clinical Practice 80 ( 1 ) 2008

Vaspin and insulin resistance

Wada, J.

Rinsho byori. The Japanese journal of clinical pathology 56 ( 8 ) 2008

Association of single-nucleotide polymorphisms in MTMR9 gene with obesity Reviewed

Takahiro Yanagiya, Atsushi Tanabe, Aritoshi Iida, Susumu Saito, Akihiro Sekine, Atsushi Takahashi, Tatsuhiko Tsunoda, Seika Kamohara, Yoshio Nakata, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Hiroaki Masuzaki, Masato Yoneda, Atsushi Nakajima, Shigeru Miyazaki, Katsuto Tokunaga, Manabu Kawamoto, Tohru Funahashi, Kazuyuki Hamaguchi, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Kazuwa Nakao, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura, Kikuko Hotta

HUMAN MOLECULAR GENETICS 16 ( 24 ) 3017 - 3026 2007.12

Collectrin, a homologue of ACE2, its transcriptional control and functional perspectives Reviewed

Yanling Zhang, Jun Wada

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 363 ( 1 ) 1 - 5 2007.11

Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells Reviewed

Kazuyoshi Omori, Yasushi Shikata, Kei Sarai, Naomi Watanabe, Jun Wada, Noriko Goda, Noriyuki Kataoka, Kenichi Shikata, Hirofumi Makino

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 293 ( 5 ) C1523 - C1531 2007.11

Linkage between oxygen uptake at ventilatory threshold and muscle strength in subjects with and without metabolic syndrome Reviewed

Nobuyuki Miyatake, Takeshi Saito, Jun Wada, Hidetaka Nishikawa, Sumiko Matsumoto, Motohiko Miyachi, Masafumi Fujii, Hirofumi Makino, Takeyuki Numata

ACTA MEDICA OKAYAMA 61 ( 5 ) 255 - 259 2007.10

Comparison of ventilatory threshold and exercise habits between Japanese men with and without metabolic syndrome Reviewed

Nobuyuki Miyatake, Takeshi Saito, Jun Wada, Motohiko Miyachi, Izumi Tabata, Sumiko Matsumoto, Hidetaka Nishikawa, Hirofumi Makino, Takeyuki Numata

DIABETES RESEARCH AND CLINICAL PRACTICE 77 ( 2 ) 314 - 319 2007.8

Re-evaluation of waist circumference in metabolic syndrome: A comparison between Japanese men and women Reviewed

Nobuyuki Miyatake, Jun Wada, Sumiko Matsumoto, Hidetaka Nishikawa, Hirofumi Makino, Takeyuki Numata

ACTA MEDICA OKAYAMA 61 ( 3 ) 167 - 169 2007.6

Urinary PGDS levels are associated with vascular injury in type 2 diabetes patients Reviewed

Ritsuko Yoshikawa, Jun Wada, Kousuke Seiki, Takashi Matsuoka, Satoshi Miyamoto, Kenji Takahashi, Sachiko Ota, Kazuhi Taniai, Kazuyuki Hida, Minoru Yamakado, Kenichi Shikata, Yoshio Uehara, Yoshihiro Urade, Hirofumi Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 76 ( 3 ) 358 - 367 2007.6

The Role for HNF-1 beta-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells Reviewed

Yanling Zhang, Jun Wada, Akihiro Yasuhara, Izumi Iseda, Jun Eguchi, Kenji Fukui, Qin Yang, Kazuya Yamagata, Thomas Hiesberger, Peter Igarashi, Hong Zhang, Haiyan Wang, Shigeru Akagi, Yashpal S. Kanwar, Hirofumi Makino

PLOS ONE 2 ( 5 ) 2007.5

Comparison of muscle strength between Japanese men with and without metabolic syndrome Reviewed

Nobuyuki Miyatake, Jun Wada, Takeshi Saito, Hidetaka Nishikawa, Sumiko Matsumoto, Motohiko Miyachi, Hirofumi Makino, Takeyuki Numata

ACTA MEDICA OKAYAMA 61 ( 2 ) 99 - 102 2007.4

Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-kappa B activation Reviewed

Sakiko Ohga, Kenichi Shikata, Kosuke Yozai, Shinichi Okada, Daisuke Ogawa, Hitomi Usui, Jun Wada, Yasushi Shikata, Hirofumi Makino

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 292 ( 4 ) F1141 - F1150 2007.4

Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-κB activation Reviewed

Sakiko Ohga, Kenichi Shikata, Kosuke Yozai, Shinichi Okada, Daisuke Ogawa, Hitomi Usui, Jun Wada, Yasushi Shikata, Hirofumi Makino

American Journal of Physiology - Renal Physiology 292 ( 4 ) F1141 - F1150 2007.4

Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity Reviewed

Atsushi Tanabe, Takahiro Yanagiya, Aritoshi Iida, Susumu Saito, Akihiro Sekine, Atsushi Takahashi, Takahiro Nakamura, Tatsuhiko Tsunoda, Seika Kamohara, Yoshio Nakata, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Kazuyuki Hamaguchi, Tatsuo Shimada, Kiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura, Kikuko Hotta

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 92 ( 3 ) 1145 - 1154 2007.3

Changes of gene expression profiles in macrophages stimulated by angiotensin II - Angiotensin II induces MCP-2 through AT(1)-receptor Reviewed

Atsuhito Tone, Kenichi Shikata, Daisuke Ogawa, Sakiko Sasaki, Ryo Nagase, Motofumi Sasaki, Kosuke Yozai, Hitomi Kataoka Usui, Shinichi Okada, Jun Wada, Yasushi Shikata, Hirofumi Makino

JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM 8 ( 1 ) 45 - 50 2007.3

Macrophage scavenger receptor-A-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation Reviewed

Hitorni Kataoka Usui, Kenichi Shikata, Motofurni Sasaki, Shinichi Okada, Mitsuhiro Matsuda, Yasushi Shikata, Daisuke Ogawa, Yuichi Kido, Ryo Nagase, Kosuke Yozai, Sakiko Ohga, Atsuhito Tone, Jun Wada, Masahiro Takeya, Seikoh Horiuchi, Tatsuhiko Kodama, Hirofunti Makino

DIABETES 56 ( 2 ) 363 - 372 2007.2

Serpins and the metabolic syndrome Reviewed

Jun Wada

Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity 411 - 423 2007.1

Hemophagocytic syndrome associated with fatal veno-occlusive disease in the liver Reviewed

Atsuko Nakatsuka, Jun Wada, Ryo Nagase, Masaya Takeda, Tadashi Yoshino, Hirofumi Makino

INTERNAL MEDICINE 46 ( 8 ) 495 - 499 2007

Severe hypoglycemia induced by IGF-II producing non-islet cell tumor

Kanzaki, M., Kashihara, H., Kiura, K., Murakami, K., Iwagaki, H., Wada, J., Makino, H.

Internal Medicine 46 ( 13 ) 1061 - 1061 2007

Hypolipidemia of renal diseases

Teshigawara, S., Wada, J., Makino, H.

Nippon rinsho. Japanese journal of clinical medicine 65 Suppl 7 2007

Erratum: Macrophage scavenger receptor-A - Deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation (Diabetes (2007) 56, (263-372))

Usui, H.K., Shikata, K., Sasaki, M., Okada, S., Matsuda, M., Shikata, Y., Ogawa, D., Kido, Y., Nagase, R., Yozai, K., Ohga, S., Tone, A., Wada, J., Takeya, M., Horiuchi, S., Kodama, T., Makino, H.

Diabetes 56 ( 3 ) 897 - 897 2007

Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms Reviewed

T Okada, J Wada, K Hida, J Eguchi, Hashimoto, I, M Baba, A Yasuhara, K Shikata, H Makino

DIABETES 55 ( 6 ) 1666 - 1677 2006.6

Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects Reviewed

Izumi Hashimoto, Jun Wada, Aya Hida, Masako Baba, Nobuyuki Miyatake, Jun Eguchi, Kenichi Shikata, Hirofumi Makino

OBESITY 14 ( 5 ) 799 - 811 2006.5

Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects Reviewed

Izumi Hashimoto, Jun Wada, Aya Hida, Masako Baba, Nobuyuki Miyatake, Jun Eguchi, Kenichi Shikata, Hirofumi Makino

Obesity 14 ( 5 ) 799 - 811 2006.5

Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production Reviewed

Yanling Zhang, Jun Wada, Izumi Hashimoto, Jun Eguchi, Akihiro Yasuhara, Yashpal S. Kanwar, Kenichi Shikata, Hirofumi Makino

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 17 ( 4 ) 1090 - 1101 2006.4

The application of synthetic hANP in diabetic nephropathy with nephrotic syndrome Reviewed

Y Kikumoto, J Wada, H Makino

DIABETES CARE 29 ( 1 ) 172 - 173 2006.1

Relationship between metabolic syndrome and cigarette smoking in the Japanese population Reviewed

Nobuyuki Miyatake, Jun Wada, Yuriko Kawasaki, Kenji Nishii, Hirofumi Makino, Takeyuki Numata

INTERNAL MEDICINE 45 ( 18 ) 1039 - 1043 2006

Relationship between metabolic syndrome and proteinuria in the Japanese population Reviewed

Nobuyuki Miyatake, Jun Wada, Yuriko Kawasaki, Sumiko Matsumoto, Hirofumi Makino, Takeyuki Numata

INTERNAL MEDICINE 45 ( 9 ) 599 - 603 2006

Molecular biology of regulation in renal functions; biosynthesis, metabolism, and action of insulin and glucagon

Nakatsuka, A., Wada, J., Makino, H.

Nippon rinsho. Japanese journal of clinical medicine 64 Suppl 2 2006

ACAM, vaspin

Wada, J., Hida, K., Eguchi, J., Makino, H.

Nippon rinsho. Japanese journal of clinical medicine 64 Suppl 9 2006

The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation Reviewed

K Fukui, Q Yang, Y Cao, N Takahashi, H Hatakeyama, HY Wang, J Wada, YL Zhang, L Marselli, T Nammo, K Yoneda, M Onishi, S Higashiyama, Y Matsuzawa, FJ Gonzalez, GC Weir, H Kasai, L Shimomura, J Miyagawa, CB Wollheim, K Yamagata

CELL METABOLISM 2 ( 6 ) 373 - 384 2005.12

Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients Reviewed

H Morimoto, K Nakao, K Fukuoka, A Sarai, A Yano, T Kihara, S Fukuda, J Wada, H Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 20 ( 12 ) 2775 - 2782 2005.12

Modulation of renal-specific oxidoreductase/myo-inositol oxygenase by high-glucose ambience Reviewed

B Nayak, P Xie, S Akagi, QW Yang, L Sun, J Wada, A Thakur, FR Danesh, SS Chugh, YS Kanwar

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 102 ( 50 ) 17952 - 17957 2005.12

Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes Reviewed

A Nakamura, K Shikata, M Hiramatsu, T Nakatou, T Kitamura, J Wada, T Itoshima, H Makino

DIABETES CARE 28 ( 12 ) 2890 - 2895 2005.12

Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions Reviewed

K Yozai, K Shikata, M Sasaki, A Tone, S Ohga, H Usui, S Okada, J Wada, R Nagase, D Ogawa, Y Shikata, H Makino

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 16 ( 11 ) 3326 - 3338 2005.11

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats Reviewed

A Tone, K Shikata, M Sasaki, S Ohga, K Yozai, S Nishishita, H Usui, R Nagase, D Ogawa, S Okada, Y Shikata, J Wada, H Makino

DIABETOLOGIA 48 ( 11 ) 2402 - 2411 2005.11

Galectin-9 inhibits glomerular hypertrophy in db/db diabetic mice via cell-cycle-dependent mechanisms Reviewed

M Baba, J Wada, J Eguchi, Hashimoto, I, T Okada, A Yasuhara, K Shikata, YS Kanwar, H Makino

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 16 ( 11 ) 3222 - 3234 2005.11

Gene delivery of Tim44 reduces mitochondrial superoxide production and ameliorates neointimal proliferation of injured carotid artery in diabetic rats Reviewed

T Matsuoka, J Wada, Hashimoto, I, YL Zhang, J Eguchi, N Ogawa, K Shikata, YS Kanwar, H Makino

DIABETES 54 ( 10 ) 2882 - 2890 2005.10

Renal-specific oxidoreductase biphasic expression under high glucose ambience during fetal versus neonatal development Reviewed

YS Kanwar, S Akagi, B Nayak, L Sun, J Wada, P Xie, A Thakur, SS Chugh, FR Danesh

KIDNEY INTERNATIONAL 68 ( 4 ) 1670 - 1683 2005.10

Clinical features of non-diabetic renal diseases in patients with type 2 diabetes Reviewed

A Tone, K Shikata, M Matsuda, H Usui, S Okada, D Ogawa, J Wada, H Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 69 ( 3 ) 237 - 242 2005.9

Hyperglycemia: its imminent effects on mammalian nephrogenesis Reviewed

YS Kanwar, B Nayak, S Lin, S Akagi, P Xie, J Wada, SS Chugh, FR Danesh

PEDIATRIC NEPHROLOGY 20 ( 7 ) 858 - 866 2005.7

Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity Reviewed

K Hida, J Wada, J Eguchi, H Zhang, M Baba, A Seida, L Hashimoto, T Okada, A Yasuhara, A Nakatsuka, K Shikata, S Hourai, J Futami, E Watanabe, Y Matsuki, R Hiramatsu, S Akagi, H Makino, YS Kanwar

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 102 ( 30 ) 10610 - 10615 2005.7

Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity Reviewed

J Eguchi, J Wada, K Hida, H Zhang, T Matsuoka, M Baba, Hashimoto, I, K Shikata, N Ogawa, H Makino

BIOCHEMICAL JOURNAL 387 343 - 353 2005.4

Cell biology of diabetic kidney disease

Kanwar, YS, Akagi, S, Sun, L, Nayak, B

Nephron Experimental Nephrology 101 ( 3 ) 2005

Sulfated hyaluronic acid, a potential selectin inhibitor, ameliorates experimentally induced crescentic glomerulonephritis Reviewed

D Ogawa, K Shikata, M Matsuda, K Akima, M Iwahashi, S Okada, Y Tsuchiyama, Y Shikata, J Wada, H Makino

NEPHRON EXPERIMENTAL NEPHROLOGY 99 ( 1 ) E26 - E32 2005

Pathological roles of advanced glycation end product receptors SR-A and CD36 Reviewed

S Horiuchi, Y Unno, H Usui, K Shikata, K Takaki, W Koita, YI Sakamoto, R Nagai, K Makino, A Sasao, J Wada, H Makino

MAILLARD REACTION: CHEMISTRY AT THE INTERFACE OF NUTRITION, AGING, AND DISEASE 1043 671 - 675 2005

Cell biology of diabetic kidney disease

Kanwar, Y.S., Akagi, S., Sun, L., Nayak, B., Xie, P., Wada, J., Chugh, S.S., Danesh, F.R.

Nephron - Experimental Nephrology 101 ( 3 ) 2005

The critical role of Src homology domain 2-containing tyrosine phosphatase-1 in recombinant human erythropoietin hyporesponsive anemia in chronic hemodialysis patients Reviewed

S Akagi, H Ichikawa, T Okada, A Sarai, T Sugimoto, H Morimoto, T Kihara, A Yano, K Nakao, Y Nagake, J Wada, H Makino

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 15 ( 12 ) 3215 - 3224 2004.12

Changes in serum leptin concentrations in overweight Japanese men after exercise Reviewed

N Miyatake, K Takahashi, J Wada, H Nishikawa, A Morishita, H Suzuki, M Kunitomi, H Makino, S Kira, M Fujii

DIABETES OBESITY & METABOLISM 6 ( 5 ) 332 - 337 2004.9

Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis Reviewed

YS Kanwar, J Wada, S Lin, FR Danesh, SS Chugh, QW Yang, T Banerjee, JW Lomasney

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 286 ( 2 ) F202 - F215 2004.2

The role of adrenomedullin and receptors in glomerular hyperfiltration in streptozotocin-induced diabetic rats Reviewed

K Hiragushi, J Wada, J Eguchi, T Matsuoka, A Yasuhara, Hashimoto, I, T Yamashita, K Hida, Y Nakamura, K Shikata, N Minamino, K Kangawa, H Makino

KIDNEY INTERNATIONAL 65 ( 2 ) 540 - 550 2004.2

Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction Reviewed

D Ogawa, K Shikata, K Honke, S Sato, M Matsuda, R Nagase, A Tone, S Okada, H Usui, J Wada, M Miyasaka, H Kawashima, Y Suzuki, T Suzuki, N Taniguchi, Y Hirahara, K Tadano-Aritomi, Ishizuka, I, TF Tedder, H Makino

JOURNAL OF BIOLOGICAL CHEMISTRY 279 ( 3 ) 2085 - 2090 2004.1

Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion: Does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury? Reviewed

A Seida, J Wada, Y Morita, M Baba, J Eguchi, N Nishimoto, T Okino, K Ichimura, T Yoshino, H Makino

AMERICAN JOURNAL OF KIDNEY DISEASES 43 ( 1 ) 2004.1

Intravenous vitamin D therapy reduces PTH-(1-84)/large C fragments ratio in chronic hemodialysis patients Reviewed

T Kihara, H Ichikawa, H Morimoto, A Yano, S Akagi, K Nakao, H Kohmoto, J Wada, Kumagai, I, H Makino

NEPHRON CLINICAL PRACTICE 98 ( 3 ) C93 - C100 2004

Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion: does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury?

Seida, A., Wada, J., Morita, Y., Baba, M., Eguchi, J., Nishimoto, N., Okino, T., Ichimura, K., Yoshino, T., Makino, H.

American journal of kidney diseases : the official journal of the National Kidney Foundation 43 ( 1 ) 2004

Daily exercise lowers blood pressure and reduces visceral adipose tissue areas in overweight Japanese men Reviewed

N Miyatake, K Takahashi, J Wada, H Nishikawa, A Morishita, H Suzuki, M Kunitomi, H Makino, S Kira, M Fujii

DIABETES RESEARCH AND CLINICAL PRACTICE 62 ( 3 ) 149 - 157 2003.12

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education Reviewed

A Seida, J Wada, M Kunitomi, Y Tsuchiyama, N Miyatake, M Fujii, S Kira, K Takahashi, K Shikata, H Makino

INTERNATIONAL JOURNAL OF OBESITY 27 ( 11 ) 1325 - 1331 2003.11

Pathogenesis of IgA nephropathy Reviewed

J Wada, H Sugiyama, H Makino

SEMINARS IN NEPHROLOGY 23 ( 6 ) 556 - 563 2003.11

Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes Reviewed

S Okada, K Shikata, M Matsuda, D Ogawa, H Usui, Y Kido, R Nagase, J Wada, Y Shikata, H Makino

DIABETES 52 ( 10 ) 2586 - 2593 2003.10

Pelvic lymphocyst infection associated with maternally inherited diabetes mellitus Reviewed

D Ogawa, K Shikata, M Matsuda, J Wada, H Uchida, M Asada, H Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 61 ( 2 ) 137 - 141 2003.8

Gene regulation of aldose-, aldehyde- and a renal specific oxido reductase (RSOR) in the pathobiology of diabetes mellitus Reviewed

FR Danesh, J Wada, EI Wallner, A Sahai, SK Srivastava, YS Kanwar

CURRENT MEDICINAL CHEMISTRY 10 ( 15 ) 1399 - 1406 2003.8

Remission and regression of diabetic nephropathy Reviewed

H Makino, Y Nakamura, J Wada

HYPERTENSION RESEARCH 26 ( 7 ) 515 - 519 2003.7

Glomerular cell apoptosis in human lupus nephritis Reviewed

H Makino, H Sugiyama, Y Yamasaki, Y Maeshima, J Wada, N Kashihara

VIRCHOWS ARCHIV 443 ( 1 ) 67 - 77 2003.7

Successful treatment of necrotizing fasciitis associated with diabetic nephropathy Reviewed

D Ogawa, K Shikata, J Wada, M Matsuda, H Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 60 ( 3 ) 213 - 216 2003.6

Imprinted mesodermal specific transcript (MEST) and H19 genes in renal development and diabetes Reviewed

YS Kanwar, XM Pan, S Lin, A Kumar, J Wada, CS Haas, G Liau, JW Lomasney

KIDNEY INTERNATIONAL 63 ( 5 ) 1658 - 1670 2003.5

Perturbation of autocrine/paracrine loops of burst-forming units of erythroid-derived cells in rHuEPO-hyporesponsive hemodialysis patients Reviewed

K Nakao, J Wada, K Ota, H Ichikawa, S Akagi, A Okamoto, K Hida, Y Nagake, H Makino

AMERICAN JOURNAL OF KIDNEY DISEASES 41 ( 3 ) 624 - 636 2003.3

HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats Reviewed

H Usui, K Shikata, M Matsuda, S Okada, D Ogawa, T Yamashita, K Hida, M Satoh, J Wada, H Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 18 ( 2 ) 265 - 272 2003.2

Erratum: HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats (Nephrology Dialysis Transplantation (2003) vol. 18 (265-272))

Usui, H., Shikata, K., Matsuda, M., Okada, S., Ogawa, D., Yamashita, T., Hida, K., Satoh, M., Wada, J., Makino, H.

Nephrology Dialysis Transplantation 18 ( 7 ) 1418 - 1418 2003

Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats Reviewed

D Ogawa, K Shikata, M Matsuda, S Okada, H Usui, J Wada, N Taniguchi, H Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 17 ( 12 ) 2117 - 2121 2002.12

Daily walking reduces visceral adipose tissue areas and improves insulin resistance in Japanese obese subjects Reviewed

N Miyatake, H Nishikawa, A Morishita, M Kunitomi, J Wada, H Suzuki, K Takahashi, H Makino, S Kira, M Fujii

DIABETES RESEARCH AND CLINICAL PRACTICE 58 ( 2 ) 101 - 107 2002.11

Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis Reviewed

M Matsuda, K Shikata, F Shimizu, Y Suzuki, M Miyasaka, H Kawachi, H Kawashima, J Wada, H Sugimoto, Y Shikata, D Ogawa, SJ Tojo, K Akima, H Makino

JOURNAL OF PATHOLOGY 198 ( 3 ) 407 - 414 2002.11

Beraprost sodium, prostacyclin analogue, attenuates glomerular hyperfiltration and glomerular macrophage infiltration by modulating ecNOS expression in diabetic rats Reviewed

T Yamashita, K Shikata, M Matsuda, S Okada, D Ogawa, H Sugimoto, J Wada, H Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 57 ( 3 ) 149 - 161 2002.9

A case of congenital generalized lipodystrophy with lipoatrophic diabetes developing anti-insulin antibodies Reviewed

H Usui, K Shikata, J Wada, T Sugimoto, J Yamana, T Oishi, M Matsuda, M Yoneda, Koshima, I, H Makino

DIABETIC MEDICINE 19 ( 9 ) 794 - 795 2002.9

Isolation and functional analysis of mouse UbA52 gene and its relevance to diabetic nephropathy Reviewed

L Sun, XM Pan, J Wada, CS Haas, RP Wuthrich, FR Danesh, SS Chugh, YS Kanwar

JOURNAL OF BIOLOGICAL CHEMISTRY 277 ( 33 ) 29953 - 29962 2002.8

Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis Reviewed

D Ogawa, K Shikata, M Matsuda, S Okada, J Wada, S Yamaguchi, Y Suzuki, M Miyasaka, S Tojo, H Makino

CLINICAL AND EXPERIMENTAL IMMUNOLOGY 129 ( 1 ) 43 - 53 2002.7

Identification of developmentally regulated mesodermal-specific transcript in mouse embryonic metanephros Reviewed

YS Kanwar, A Kumar, K Ota, S Lin, J Wada, S Chugh, EI Wallner

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 282 ( 5 ) F953 - F965 2002.5

Minimal change nephrotic syndrome developing during postoperative interferon-beta therapy for malignant melanoma Reviewed

K Nakao, H Sugiyama, E Makino, H Matsuura, A Ohmoto, T Sugimoto, H Ichikawa, J Wada, Y Yamasaki, H Makino

NEPHRON 90 ( 4 ) 498 - 500 2002.4

Relevance of renal-specific oxidoreductase in tubulogenesis during mammalian nephron development Reviewed

YS Kanwar, QW Yang, YF Tian, S Lin, J Wada, S Chugh, SK Srivastava

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 282 ( 4 ) F752 - F762 2002.4

Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men Reviewed

M Kunitomi, J Wada, K Takahashi, Y Tsuchiyama, Y Mimura, K Hida, N Miyatake, M Fujii, S Kira, K Shikata, H Makino

INTERNATIONAL JOURNAL OF OBESITY 26 ( 3 ) 361 - 369 2002.3

Angiocentric immunoproliferative lesions of the lung associated with diffuse renal involvement Reviewed

S Okada, J Wada, T Tsukinoki, N Hirano, Y Watanabe, K Shikata, Y Yamasaki, S Takase, T Yoshino, T Akagi, H Makino

AMERICAN JOURNAL OF KIDNEY DISEASES 39 ( 3 ) 2002.3

Cyanotic congenital heart disease associated with glomerulomegaly and focal segmental glomerulosclerosis: Remission of nephrotic syndrome with angiotensin converting enzyme inhibitor Reviewed

K Hida, J Wada, H Yamasaki, Y Nagake, H Zhang, H Sugiyama, K Shikata, H Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 17 ( 1 ) 144 - 147 2002.1

Gene expression and identification of gene therapy targets in diabetic nephropathy Reviewed

Jun Wada, Hirofumiand Makino, Yashpal S. Kanwar

Kidney International 61 ( 1 ) S73 - S78 2002

Relevance of extracellular matrix and its receptors in mammalian nephrogenesis revealed by metanephric organ culture system Reviewed

J Wada, YS Kanwar, H Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 17 75 - 77 2002

Renal gene expression in embryonic and newborn diabetic mice Reviewed

EI Wallner, J Wada, S Lin, XM Pan, JK Reddy, SS Chugh, YS Kanwar

EXPERIMENTAL NEPHROLOGY 10 ( 2 ) 130 - 138 2002

Identification of developmentally regulated mesodermal-specific transcript in mouse embryonic metanephros Reviewed

Yashpal S. Kanwar, Anil Kumar, Kosuke Ota, Sun Lin, Jun Wada, Sumant Chugh, Elisabeth I. Wallner

American Journal of Physiology - Renal Physiology 282 ( 5 ) F953 - F965 2002

Relevance of renal-specific oxidoreductase in tubulogenesis during mammalian nephron development Reviewed

Yashpal S. Kanwar, Qiwei Yang, Yufeng Tian, Sun Lin, Jun Wada, Sumant Chugh, Satish K. Srivastava

American Journal of Physiology - Renal Physiology 282 ( 4 ) F752 - F762 2002

History of nephrology in the past 100 years: Collagen disease and vasculitis

Makino, H., Wada, J.

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 91 ( 5 ) 2002

Angiocentric immunoproliferative lesions of the lung associated with diffuse renal involvement.

Okada, S., Wada, J., Tsukinoki, T., Hirano, N., Watanabe, Y., Shikata, K., Yamasaki, Y., Takase, S., Yoshino, T., Akagi, T., Makino, H.

American journal of kidney diseases : the official journal of the National Kidney Foundation 39 ( 3 ) 2002

Management of diabetic nephropathy with nephrotic syndrome

Eguchi, J., Wada, J., Makino, H.

Nippon rinsho. Japanese journal of clinical medicine 60 Suppl 10 2002

Proteoglycans

Makino, H., Wada, J.

Nippon rinsho. Japanese journal of clinical medicine 60 Suppl 8 2002

Identification of up-regulated Ras-like GTPase, Rap1b, by suppression subtractive hybridization Reviewed

S Lin, S Chugh, XM Pan, EI Wallner, J Wada, YS Kanwar

KIDNEY INTERNATIONAL 60 ( 6 ) 2129 - 2141 2001.12

Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes Reviewed

K Hiragushi, H Sugimoto, K Shikata, T Yamashita, N Miyatake, Y Shikata, J Wada, Kumagai, I, M Fukushima, H Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 53 ( 3 ) 149 - 159 2001.9

Ultrastructure of glomerular basement membrane in active Heymann nephritis rats revealed by tissue-negative staining method Reviewed

Y Hayashi, K Hironaka, K Shikata, S Ogawa, K Ota, J Wada, K Kamata, Z Ota, H Makino

AMERICAN JOURNAL OF NEPHROLOGY 21 ( 3 ) 249 - 255 2001.5

Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys Reviewed

H Zhang, J Wada, K Hida, Y Tsuchiyama, K Hiragushi, K Shikata, HY Wang, S Lin, YS Kanwar, H Makino

JOURNAL OF BIOLOGICAL CHEMISTRY 276 ( 20 ) 17132 - 17139 2001.5

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis Reviewed

J Wada, H Zhang, Y Tsuchiyama, K Hiragushi, K Hida, K Shikata, YS Kanwar, H Makino

KIDNEY INTERNATIONAL 59 ( 4 ) 1363 - 1373 2001.4

Galectins, galactoside-binding mammalian lectins: Clinical application of multi-functional proteins Reviewed

J Wada, H Makino

ACTA MEDICA OKAYAMA 55 ( 1 ) 11 - 17 2001.2

Status of glucose transporters in the mammalian kidney and renal development Reviewed

EI Wallner, J Wada, G Tramonti, S Lin, YS Kanwar

RENAL FAILURE 23 ( 3-4 ) 301 - 310 2001

Relevance of aldo-keto reductase family members to the pathobiology of diabetic nephropathy and renal development Reviewed

EI Wallner, J Wada, G Tramonti, S Lin, SK Srivastava, YS Kanwar

RENAL FAILURE 23 ( 3-4 ) 311 - 320 2001

Diagnosis and treatment of diabetic nephropathy

Makino, H., Shikata, K., Wada, J.

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 90 ( 2 ) 2001

The necessity of renal biopsies in the management of diabetic nephropathy

Makino, H., Wada, J., Matsuda, M.

Internal Medicine 40 ( 11 ) 2001

Successful use of cyclosporin A for the treatment of acute interstitial pneumonitis associated with rheumatoid arthritis Reviewed

D Ogawa, H Hashimoto, J Wada, A Ueno, Y Yamasaki, M Yamamura, H Makino

RHEUMATOLOGY 39 ( 12 ) 1422 - 1424 2000.12

Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats Reviewed

Y Tsuchiyama, J Wada, H Zhang, Y Morita, K Hiragushi, K Hida, K Shikata, M Yamamura, YS Kanwar, H Makino

KIDNEY INTERNATIONAL 58 ( 5 ) 1941 - 1952 2000.11

Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats Reviewed

K Hida, J Wada, H Zhang, K Hiragushi, Y Tsuchiyama, K Shikata, H Makino

JOURNAL OF LIPID RESEARCH 41 ( 10 ) 1615 - 1622 2000.10

Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold Reviewed

M Kunitomi, K Takahashi, J Wada, H Suzuki, N Miyatake, S Ogawa, S Ohta, H Sugimoto, K Shikata, H Makino

DIABETES RESEARCH AND CLINICAL PRACTICE 50 ( 2 ) 109 - 115 2000.10

Expression characteristics and relevance of sodium glucose cotransporter-1 in mammalian renal tubulogenesis Reviewed

QW Yang, YF Tian, J Wada, N Kashihara, E Wallner, D Peterson, YS Kanwar

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 279 ( 4 ) F765 - F777 2000.10

Familial interstitial nephritis with progressive renal failure Reviewed

H Zhang, J Wada, K Nanba, M Kunitomi, K Hida, Y Nagake, K Shikata, H Makino

AMERICAN JOURNAL OF KIDNEY DISEASES 36 ( 4 ) art. no. - e25 2000.10

Identification of a renal-specific oxido-reductase in newborn diabetic mice Reviewed

QW Yang, B Dixit, J Wada, YF Tian, EI Wallner, SK Srivastva, YS Kanwar

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 97 ( 18 ) 9896 - 9901 2000.8

Clinical evaluation of muscle strength in 20-79-years-old obese Japanese Reviewed

N Miyatake, M Fujii, H Nishikawa, J Wada, K Shikata, H Makino, Kimura, I

DIABETES RESEARCH AND CLINICAL PRACTICE 48 ( 1 ) 15 - 21 2000.4

Malignant hypertension with a rare complication of pulmonary alveolar hemorrhage Reviewed

K Hida, J Wada, M Odawara, M Kunitomi, N Hayakawa, N Kashihara, H Makino

AMERICAN JOURNAL OF NEPHROLOGY 20 ( 1 ) 64 - 67 2000.1

Fatal pancreatitis associated with systemic amyloidosis in a rheumatoid arthritis patient Reviewed

Kazuhiro Oishi, Jun Wada, Yoshio Nagake, Kazuyuki Hida, Hiroo Hashimoto, Nobuaki Hayakawa, Naoki Kashihara, Hirofumi Makino

Journal of Medicine 31 ( 5-6 ) 303 - 310 2000

Familial interstitial nephritis with progressive renal failure.

Zhang, H., Wada, J., Nanba, K., Kunitomi, M., Hida, K., Nagake, Y., Shikata, K., Makino, H.

American journal of kidney diseases : the official journal of the National Kidney Foundation 36 ( 4 ) 2000

Role of membrane-type matrix metalloproteinase 1 (MT-1-MMP), MMP-2, and its inhibitor in nephrogenesis Reviewed

YS Kanwar, K Ota, QW Yang, J Wada, N Kashihara, Y Tian, EI Wallner

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 277 ( 6 ) F934 - F947 1999.12

Novel approaches to unravel the genesis of glomerulosclerosis by new methodologies in molecular biology and molecular genetics Reviewed

J Wada, K Shikata, H Makino

NEPHROLOGY DIALYSIS TRANSPLANTATION 14 ( 11 ) 2551 - 2553 1999.11

Tubulointerstitial nephritis antigen: An extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development Reviewed

YS Kanwar, A Kumar, QW Yang, YF Tian, J Wada, N Kashihara, EI Wallner

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 96 ( 20 ) 11323 - 11328 1999.9

Integrins mediate the inhibitory effect of focal adhesion on angiotensin II-induced p44/42 mitogen-activated protein (MAP) kinase activity in human mesangial cells Reviewed

Y Shikata, K Shikata, M Matsuda, K Hiragushi, D Ogawa, H Sugimoto, J Wada, H Makino

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 261 ( 3 ) 820 - 823 1999.8

Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung Reviewed

QW Yang, K Ota, YF Tian, A Kumar, J Wada, N Kashihara, E Wallner, YS Kanwar

DEVELOPMENTAL BIOLOGY 212 ( 1 ) 229 - 242 1999.8

Screening for genes up-regulated in 5/6 nephrectomized mouse kidney Reviewed

H Zhang, J Wada, YS Kanwar, Y Tsuchiyama, K Hiragushi, K Hida, K Shikata, H Makino

KIDNEY INTERNATIONAL 56 ( 2 ) 549 - 558 1999.8

Advanced glycation end products-cytokine-nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumour necrosis factor-alpha and inducible nitric oxide synthase in diabetic rat glomeruli Reviewed

H Sugimoto, K Shikata, J Wada, S Horiuchi, H Makino

DIABETOLOGIA 42 ( 7 ) 878 - 886 1999.7

L-selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction Reviewed

K Shikata, Y Suzuki, J Wada, K Hirata, M Matsuda, H Kawashima, T Suzuki, M Iizuka, H Makino, M Miyasaka

JOURNAL OF PATHOLOGY 188 ( 1 ) 93 - 99 1999.5

Signaling transduction pathway of angiotensin II in human mesangial cells: Mediation of focal adhesion and GTPase activating proteins Reviewed

Y Shikata, K Shikata, M Masuda, H Sugimoto, J Wada, H Makino

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 257 ( 1 ) 234 - 238 1999.4

Differential distribution of insulin-like growth factor-1 and insulin-like growth factor binding proteins in experimental diabetic rat kidney Reviewed

N Miyatake, K Shikata, J Wada, H Sugimoto, S Takahashi, H Makino

NEPHRON 81 ( 3 ) 317 - 323 1999.3

Increased urinary excretion of macrophage-colony-stimulating factor (M-CSF) in patients with IgA nephropathy: Tonsil stimulation enhances urinary M-CSF excretion Reviewed

M Matsuda, K Shikata, J Wada, H Yamaji, Y Shikata, A Doi, M Kosaka, H Akagi, Y Masuda, Y Ohmoto, H Makino

NEPHRON 81 ( 3 ) 264 - 270 1999.3

Renal organogenesis and extracellular matrix - Knockout mice are telling the truth? -

Wada, J., Ota, K., Kashihara, N., Kanwar, Y.S., Makino, H.

Connective Tissue 31 ( 1 ) 1999

Increased expression of endothelial cell nitric oxide synthase (ecNOS) in afferent and glomerular endothelial cells is involved in glomerular hyperfiltration of diabetic nephropathy Reviewed

H Sugimoto, K Shikata, M Matsuda, M Kushiro, Y Hayashi, K Hiragushi, J Wada, H Makino

DIABETOLOGIA 41 ( 12 ) 1426 - 1434 1998.12

Deposition of mannan binding protein and mannan binding protein-mediated complement activation in the glomeruli of patients with IgA nephropathy Reviewed

M Matsuda, K Shikata, J Wada, H Sugimoto, Y Shikata, T Kawasaki, H Makino

NEPHRON 80 ( 4 ) 408 - 413 1998.12

Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development Reviewed

YS Kanwar, K Ota, QW Yang, A Kumar, J Wada, N Kashihara, DR Peterson

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 275 ( 5 ) F710 - F723 1998.11

Relevance of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis Reviewed

EI Wallner, QW Yang, DR Peterson, J Wada, YS Kanwar

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 275 ( 4 ) F467 - F477 1998.10

A case of membranous nephropathy associated with psoriasis vulgaris Reviewed

H Yamaji, K Shikata, J Wada, Y Hayashi, S Ikeda, H Makino

NEPHRON 80 ( 1 ) 111 - 112 1998.9

Fatal hyperammonemia in a patient with systemic lupus erythematosus Reviewed

H Ichikawa, T Amano, K Kawabata, M Kushiro, J Wada, Y Nagake, H Makino

INTERNAL MEDICINE 37 ( 8 ) 700 - 703 1998.8

Ultrastructure of mesangial type III collagen deposition in a patient with IgA nephropathy Reviewed

M Kunitomi, J Wada, N Miyatake, Y Hayashi, K Ota, H Makino

AMERICAN JOURNAL OF KIDNEY DISEASES 32 ( 1 ) 146 - 152 1998.7

Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor Reviewed

K Ota, WG Stetler-Stevenson, QW Yang, A Kumar, J Wada, N Kashihara, EI Wallner, YS Kanwar

KIDNEY INTERNATIONAL 54 ( 1 ) 131 - 142 1998.7

Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat Reviewed

M Kushiro, K Shikata, H Sugimoto, Y Shikata, N Miyatake, J Wada, M Miyasaka, H Makino

KIDNEY INTERNATIONAL 53 ( 5 ) 1314 - 1320 1998.5

Characterization of mammalian translocase of inner mitochondrial membrane (Tim44) isolated from diabetic newborn mouse kidney Reviewed

J Wada, YS Kanwar

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 95 ( 1 ) 144 - 149 1998.1

Bcl-2 expression and apoptosis in nephrotoxic nephritis Reviewed

H Sugiyama, N Kashihara, T Onbe, Y Yamasaki, J Wada, T Sekikawa, K Okamoto, K Kanao, Y Maeshima, H Makino

EXPERIMENTAL NEPHROLOGY 5 ( 6 ) 481 - 489 1997.11

Role of extracellular matrix, growth factors and proto-oncogenes in metanephric development Reviewed

YS Kanwar, FA Carone, A Kumar, J Wada, K Ota, EI Wallner

KIDNEY INTERNATIONAL 52 ( 3 ) 589 - 606 1997.9

Developmental regulation and partial-length cloning of tubulointerstitial nephritis antigen of murine metanephros Reviewed

A Kumar, K Ota, J Wada, EI Wallner, AS Charonis, FA Carone, YS Kanwar

KIDNEY INTERNATIONAL 52 ( 3 ) 620 - 627 1997.9

Representational difference analysis of cDNA of genes expressed in embryonic kidney Reviewed

J Wada, A Kumar, K Ota, EI Wallner, DC Batlle, YS Kanwar

KIDNEY INTERNATIONAL 51 ( 5 ) 1629 - 1638 1997.5

Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin Reviewed

J Wada, K Ota, A Kumar, EI Wallner, YS Kanwar

JOURNAL OF CLINICAL INVESTIGATION 99 ( 10 ) 2452 - 2461 1997.5

Identification and characterization of galectin-9, a novel beta-galactoside-binding mammalian lectin Reviewed

J Wada, YS Kanwar

JOURNAL OF BIOLOGICAL CHEMISTRY 272 ( 9 ) 6078 - 6086 1997.2

D-glucose-induced dysmorphogenesis of embryonic kidney Reviewed

YS Kanwar, ZZ Liu, A Kumar, MI Usman, J Wada, EI Wallner

JOURNAL OF CLINICAL INVESTIGATION 98 ( 11 ) 2478 - 2488 1996.12

Comparative role of phosphotyrosine kinase domains of c-ros and c-ret protooncogenes in metanephric development with respect to growth factors and matrix morphogens Reviewed

ZZ Liu, J Wada, A Kumar, FA Carone, M Takahashi, YS Kanwar

DEVELOPMENTAL BIOLOGY 178 ( 1 ) 133 - 148 1996.8

The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats Reviewed

J Wada, K Shikata, H Makino, S Morioka, K Hirata, K Ota, T Tamatani, M Miyasaka, T Horiuchi, S Noji, K Nishikawa, F Myokai, S Taniguchi, YS Kanwar, Z Ota

NEPHRON 73 ( 2 ) 264 - 272 1996.6

Cloning of mouse integrin alpha(V) cDNA and role of the alpha(V)-related matrix receptors in metanephric development Reviewed

J Wada, A Kumar, Z Liu, E Ruoslahti, L Reichardt, J Marvaldi, YS Kanwar

JOURNAL OF CELL BIOLOGY 132 ( 6 ) 1161 - 1176 1996.3

The Critical Role of Intercellular Adhesion Molecule-1 in Masugi Nephritis in Rats

Jun Wada

Nephron Clinical Practice 73 ( 2 ) 1996

Erratum: Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins (Kidney Int (48: 1646-1659))

Kanwar, Y.S., Liu, Z.Z., Kumar, A., Wada, J., Carone, F.A.

Kidney International 49 ( 1 ) 306 - 306 1996

CLONING OF MOUSE C-ROS RENAL CDNA, ITS ROLE IN DEVELOPMENT AND RELATIONSHIP TO EXTRACELLULAR-MATRIX GLYCOPROTEINS Reviewed

YS KANWAR, ZZ LIU, A KUMAR, J WADA, FA CARONE

KIDNEY INTERNATIONAL 48 ( 5 ) 1646 - 1659 1995.11

DISTRIBUTION OF EXTRACELLULAR-MATRIX RECEPTORS IN VARIOUS FORMS OF GLOMERULONEPHRITIS Reviewed

K SHIKATA, H MAKINO, S MORIOKA, T KASHITANI, K HIRATA, Z OTA, J WADA, YS KANWAR

AMERICAN JOURNAL OF KIDNEY DISEASES 25 ( 5 ) 680 - 688 1995.5

A case of systemic lupus erythematosus associated with severe fibrinoid necrosis located mainly in the glomerular afferent arteriole

Morioka, S., Makino, H., Wada, J., Shikata, K., Yamasaki, Y., Ogura, T., Amano, T., Asaumi, A., Okada, S., Ota, Z.

The Japanese Journal of Nephrology 37 ( 1 ) 1995

Activation of complement during hemodialysis

Nagake, Y., Amano, T., Wada, J., Sugimoto, H., Kawabata, K., Shikata, K., Makino, H., Ota, Z.

Japanese Journal of Clinical Immunology 18 ( 2 ) 1995

TROPHIC EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I ON METANEPHRIC DEVELOPMENT - RELATIONSHIP TO PROTEOGLYCANS Reviewed

ZZ LIU, A KUMAR, EI WALLNER, J WADA, FA CARONE, YS KANWAR

EUROPEAN JOURNAL OF CELL BIOLOGY 65 ( 2 ) 378 - 391 1994.12

LOCALIZATION OF FIBRIL MICROFIBRIL AND BASEMENT-MEMBRANE COLLAGENS IN DIABETIC GLOMERULOSCLEROSIS IN TYPE-2 DIABETES Reviewed

H MAKINO, K SHIKATA, J WIESLANDER, J WADA, N KASHIHARA, K YOSHIOKA, Z OTA

DIABETIC MEDICINE 11 ( 3 ) 304 - 311 1994.4

IMMUNOREACTIVITY OF THE JK-132 MONOCLONAL-ANTIBODY DIRECTED AGAINST BASEMENT-MEMBRANE COLLAGEN IN NORMAL AND DIABETIC GLOMERULI Reviewed

H MAKINO, K SHIKATA, T HAYASHI, J WIESLANDER, T HARAMOTO, K HIRATA, J WADA, T YOSHIDA, K YOSHIOKA, Z OTA

VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY 424 ( 3 ) 235 - 241 1994.4

INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR IN METANEPHRIC DEVELOPMENT Reviewed

YS KANWAR, ZZ LIU, J WADA

EXTRACELLULAR MATRIX IN THE KIDNEY 107 168 - 173 1994

A case of non-IgA mesangioproliferative glomerulonephritis with huge paramesangial hemispherical deposits

Sugimoto, H., Makino, H., Wada, J., Shikata, K.-I., Ikeda, S., Ota, Z.

the japanese journal of nephrology 35 ( 9 ) 1994

Effect of heparin and low-molecular-weight heparin on proliferative glomerulonephritis

Morita, Y., Makino, H., Ota, K., Wada, J., Shikata, K., Kashihara, N., Ikeda, S., Ogura, T., Ota, Z.

Japanese Journal of Nephrology 36 ( 7 ) 1994

DISTRIBUTION AND RELEVANCE OF INSULIN-LIKE GROWTH FACTOR-I RECEPTOR IN METANEPHRIC DEVELOPMENT Reviewed

ZZ LIU, J WADA, K ALVARES, A KUMAR, EI WALLNER, YS KANWAR

KIDNEY INTERNATIONAL 44 ( 6 ) 1242 - 1250 1993.12

CLONING OF CDNA FOR THE ALPHA-SUBUNIT OF MOUSE INSULIN-LIKE GROWTH FACTOR-I RECEPTOR AND THE ROLE OF THE RECEPTOR IN METANEPHRIC DEVELOPMENT Reviewed

J WADA, ZZ LIU, K ALVARES, A KUMAR, E WALLNER, H MAKINO, YS KANWAR

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90 ( 21 ) 10360 - 10364 1993.11

Expression of the VLA family of integrins in the renal glomerulus

Makino, H., Shikata, K., Morioka, S., Wada, J., Ota, Z.

Nihon Jinzo Gakkai Shi 35 ( 1 ) 1993

Expression of the VLA Family of Integrins in the Renal Glomerulus

Makino, H., Shikata, K., Morioka, S., Wada, J., Ota, Z.

the japanese journal of nephrology 35 ( 1 ) 1993

Clinicopathological study of patients with immune complex type and pauci immune type rapidly progressive glomerulonephritis

Sugiyama, H., Makino, H., Wada, J., Ota, K., Nagake, Y., Morioka, S., Yamasaki, Y., Shikata, K., Kashihara, N., Ikeda, S., Ogura, T., Ota, Z.

Japanese Journal of Nephrology 35 ( 6 ) 1993

Immunohistochemical study of vitronectin and membrane attack complex in normal and diseased renal tissues

Wada, J., Makino, H., Shikata, K., Morioka, S., Ota, Z.

Connective Tissue 23 ( 2 ) 1992

Distribution of a novel chain of basement membrane associated-collagen in the renal tissue

Makino, H., Haramoto, T., Shikata, K., Hirata, K., Wada, J., Morioka, S., Ota, Z., Yoshida, T., Hayashi, T.

Connective Tissue 24 ( 3 ) 1992

Plasma concentrations of vitronectin in patients with glomerulonephritis

Morioka, S., Makino, H., Shikata, K., Wada, J., Ota, Z., Uchida, M., Shimo-oka, T., Ii, I.

Connective Tissue 23 ( 3-4 ) 1992

Localization of fibronectin receptor and vitronectin receptor in the glomerulus - Comparison with their ligands

Makino, H., Shikata, K., Morioka, S., Wada, J., Ota, Z.

Connective Tissue 23 ( 2 ) 1992

A case of neuro-Behçet's disease started with diplopia

Wada, J., Amano, T., Tanokuchi, S., Ota, Z., Oshima, K., Otsuki, H., Matsuo, N.

Japanese Journal of Clinical Immunology 14 ( 4 ) 1991

A case of lupus nephritis with hyporeninemic hypoaldosteronism

Wada, J., Makino, H., Ota, Z., Yokoi, T., Nagayama, K., Asano, K., Fukushima, M.

The Japanese Journal of Nephrology 33 ( 8 ) 1991

A Case of Idiopathic Diabetes Insipidus Complicated by Diabetes Mellitus

Wada, J., Hashimoto, K., Takahashi, K., Kubota, A., Kusumoto, T., Miyake, Y.

Journal of the Japan Diabetes Society 34 ( 11 ) 1991

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