Faculty Profiles - WADA Jun

Papers - WADA Jun

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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

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