Faculty Profiles - WADA Jun

Papers - WADA Jun

Division display 441 - 460 of about 510 ／ All the affair displays >>

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

Language：English Publishing type：Research paper (scientific journal) Publisher：MARCEL DEKKER INC

Aldo-keto reductases (AKRs) are a family of monomeric oxido-reductases with molecular weight ranging from 35-40 kDa and currently includes upwards of 60 members. They are expressed in a wide variety of tissues, where they catalyze the NADPH-dependent reduction of various aliphatic and aromatic aldehydes and ketones. The functions of most of the family members are not well defined. But two members, aldehyde reductase (AKR1A) and aldose reductase (AKR1B), have been extensively studied. The latter has received the most attention since being relevant to the complications of diabetes mellitus: It is upregulated during hyperglycemia, and at the same time there is an increased activity of the sorbitol pathway aAlthough, it has no homology with other AKR members, it binds to NADPH with high affinity and is up-regulated in streptozotocin-induced diabetes in mice. It is also developmentally regulated and seems to selectively modulate renal tubulogenesis during embryonic life.nd non-enzymatic glycation of proteins with ensuing damage in various tissues. It is developmentally regulated in the ocular lens, and is believed to modulate lens fiber morphogenesis during fetal life. Unlike the other AKR family members that are ubiquitously expressed, recently a renal-specific oxio-reductase has been described that. is expressed exclusively in the proximal tubules.

DOI： 10.1081/JDI-100104715

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

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL SCIENCE INC

Background. Galectins are characterized by specific affinity for beta -galactoside sugars, and they play a role in diverse biological processes, including cell adhesion, cell proliferation, and apoptosis. Galectin-1, -3, and -9 have been implicated in modulating the immune response.
Methods. Nephrotoxic serum nephritis, which is characterized by crescent formation and glomerular influx of CD8(+) cells into glomerular capillaries, was induced in Wistar Kyoto (WKY) rats by injecting rabbit antiglomerular basement membrane serum. Following induction, the rats were treated either with phosphate-buffered saline or dexamethasone, galectin-1, galectin-3, or galectin-9 on alternate days and were sacrificed at day 14. At day 8, splenic lymphocytes were isolated and employed for terminal deoxytransferase-mediated uridine triphosphate nick end-labeling (TUNEL) assay to assess the degree of apoptosis, and the kidneys were utilized to determine the extent of influx of CD4(+) and CD8(+) cells and glomerular damage.
Results. Dexamethasone induced a marked apoptosis of splenic CD4(+) and CD8(+) cells, and it inhibited the production of anti-rabbit IgG and the influx of CD8(+) cells and macrophages into the renal glomeruli. Crescent formation and excretion of urinary proteins were also reduced. Galectin-9 failed to induce apoptosis in the CD4(+) cells; however, it induced apoptosis in the CD8(+) cells and inhibited the infiltration of CD8(+) cells. Although galectin-1 and -3 did not induce the apoptosis in the T cells, they inhibited the accumulation of macrophages in the renal glomeruli. Like dexamethasone, the galectins also reduced the crescentic formation, proliferation of glomerular cells, and excretion of urinary proteins.
Conclusions. Galectin-9 selectively induces apoptosis of the activated CD8(+) cells, while the macrophage influx into the kidney is modulated by all three galectins. This finding raises an interesting possibility for the utility of galectins in the modulation of macrophages that are involved in immune-mediated glomerular diseases.

DOI： 10.1046/j.1523-1755.2000.00366.x

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

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPID RESEARCH INC

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we con firmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed similar to 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gem family. VAT of OLETF rats had a unique gem expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI IRELAND LTD

Prescription of aerobic exercise for Type 2 diabetes mellitus (Type 2 DM) in clinical practice is frequently based on exercise intensity at maximum heart rate (60 < HRmax < 79%), heart rate reserve (50 < HRreserve < 74%), and rating of perceived exertion (12 < RPE < 13). We examined these parameters in Japanese males with Type 2 DM at ventilatory threshold (VT) to investigate the exercise capacity of Type 2 DM patients and re-evaluate the exercise prescription. Fifty-six Japanese Type ? DM males without autonomic neuropathy [age, 53.5 +/- 7.7 years; body mass index (BMI), 23.7 +/- 3.6 kg/m(2)] were enrolled and compared with 56 age- and BMI-matched healthy Japanese males. VT was determined breath by breath during exercise test using a ramp protocol and rates of oxygen consumption ((V) over dotO(2)), work rate (WR), HR, Delta HR, %HRmax '%HRreserve, and RPE were measured at VT. Type 2 DM patients had significantly lower (V) over dot O-2 (3.6 +/- 0.4 metabolic equivalents (METs)) and WR (62 +/- 14 W) than controls ((V) over dot O-2 3.9 +/- 0.6 METs; WR, 74 +/- 13 W). %HRreserve, (32.6 +/- 7.7%) was also significantly lower compared with controls (37.6+/-8.3%), while %HRmax, was not different. RPE was also similar in diabetics (12.4 +/- 1.5) and controls (12.9 +/- 1.2). however, it was significantly lower in diabetic patients aged 60-69 years (11.8 +/- 2.0) and those with distal symmetric sensory neuropathy (12.2 +/- 1.0). Our results indicate reduced exercise capacity in Japanese Type 2 DM males and the exercise intensity of 60%HRmax, 30%HRreserve, and RPE 12 is recommended in elderly diabetics and those with diabetic sensory neuropathy. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0168-8227(00)00170-4

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

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER PHYSIOLOGICAL SOC

Expression and role of sodium glucose cotransporter (SGLT-1) in tubulogenesis were investigated during renal development. A mouse SGLT-1 cDNA was cloned, and it had substantial homology with human and rat forms. Four mRNA transcripts were detected, which differed in size from other species. SGLT-1 transcripts were detected at day 13 of gestation, and their expression increased during later stages extending into the postnatal period. A high mRNA and protein expression of SGLT-1 was seen in tubular segments of the inner cortex and outer medulla at day 16, and it was developmentally regulated. Treatment with SGLT-1 antisense selectively decreased the population of tubules in the metanephric explants. Expression of glomerular mRNA and WGA binding were unchanged. SGLT-1 activity, as measured by [(14)C]methyl-alpha-D-glucopyranoside uptake, increased during gestation in the tubular segments where it is expressed. Glucose uptake was inhibited by the treatment with SGLT-1 antisense and D-galactose. The data suggest that SGLT-1 exhibits a restricted spatiotemporal expression with functional activity confined to the corresponding tubular segments, and it selectively maintains renal tubulogenesis during development.

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

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO

We describe a 53-year-old woman with chronic interstitial nephritis and asymptomatic impairment of renal function. Seven members of her family were suffering from renal failure and underwent hemodialysis. At the time of their hospital admissions, they had shown evidence of end-stage renal failure at 40 to 50 years of age. Lack of proteinuria, hematuria, hypertension, hyperuricemia, hearing loss, and visual impairment were present before the deterioration of the renal function. Renal biopsy of the presented case indicated chronic interstitial nephritis without glomerular basement membrane abnormalities. Progressive decline of renal function and the inheritance pattern of autosomal dominance in this family suggested the diagnosis of familial interstitial nephritis. (C) 2000 by the National Kidney Foundation, Inc.

DOI： 10.1053/ajkd.2000.17730

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

Language：English Publishing type：Research paper (scientific journal) Publisher：NATL ACAD SCIENCES

Aldose reductase (ALR2), a NADPH-dependent aldo-keto reductase (AKR), is widely distributed in mammalian tissues and has been implicated in complications of diabetes, including diabetic nephropathy. To identify a renal-specific reductase belonging to the AKR family, representational difference analyses of cDNA from diabetic mouse kidney were performed. A full-length cDNA with an ORF of 855 nt and yielding a approximate to 1.5-kb mRNA transcript was isolated from a mouse kidney library. Human and rat homologues also were isolated, and they had approximate to 91% and approximate to 97% amino acid identity with mouse protein. In vitro translation of the cDNA yielded a protein product of approximate to 33 kDa, Northern and Western blot analyses, using the cDNA and antirecombinant protein antibody, revealed its expression exclusively confined to the kidney. Like ALR2, the expression was up-regulated in diabetic kidneys. Its mRNA and protein expression was restricted to renal proximal tubules. The gene neither codistributed with Tamm-Horsfall protein nor aquaporin-2, The deduced protein sequence revealed an AKR-3 motif located near the N terminus, unlike the other AKR family members where it is confined to the C terminus. Fluorescence quenching and reactive blue agarose chromatography studies revealed that it binds to NADPH with high affinity (K-dNADPH = 66.9 +/- 2.3 nM). This binding domain is a tetrapeptide (Met-Ala-Lys-Ser) located within the AKR-3 motif that is similar to the other AKR members. The identified protein is designated as RSOR because it is renal-specific with properties of an oxido-reductase, and like ALR2 it may be relevant in the renal complications of diabetes mellitus.

DOI： 10.1073/pnas.160266197

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI IRELAND LTD

It is well known that obesity is closely related to non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and cardiovascular disease, and the insulin resistance associated with obesity is supposed to play a central role for the development of these diseases. Thus, effective prevention and treatment of obesity need to be explored. In 357 obese (body mass index greater than or equal to 26.4) subjects, aged 20-79 years, grip and leg strength were determined and compared with age- and sex-matched 1683 nonobese control subjects. Age-dependent alteration of body composition, evaluated by waist-hip ratio and the relative fat mass volume, was also compared. Finally, the relationship between the number of risk factors related to atherosclerosis and muscle strength was evaluated. Grip and leg strength in obese subjects were obviously stronger than controls under the age of 60 in both sexes. However, in the subjects over 60 years old, muscle strength was similar between obese subjects and controls. Weight bearing index (WBI) (leg strength (kg)/body weight (kg)) in obese subjects was remarkably lower than that in controls in all generations. In obese subjects, the waist-hip ratio and relative percentage of fat increased with aging, and obese subjects with multiple risk factors had higher waist-hip ratio and a tendency for lower muscle strength. Reduced WBI was considered to be a fundamental feature of obese subjects, and obese subjects increased fat composition with aging, which may be linked with low muscle strength. Thus, we need to design the most effective protocols to maximize and maintain quantitative and qualitative properties of muscle. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0168-8227(99)00132-1

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

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

A 34-year-old Japanese male was admitted to Okayama University Hospital with severe hypertension, rapidly progressive renal failure, blurred vision, dyspnea and hemoptysis. Clinical diagnosis of malignant hypertension was given and antihypertensive therapy and hemodialysis were immediately started. Renal biopsy was performed on the sixth day in hospital to examine the underlying disease, such as microscopic form of polyarteritis, since the complaint of hemoptysis and pulmonary alveolar hemorrhage was noted by computed tomography of the lungs. Typical pathological changes of malignant hypertension, i.e. fibrinoid necrosis of the afferent arterioles and proliferative endoarteritis at the interlobular arteries were observed. There was no evidence of active necrotizing glomerulonephritis and crescent formation. Renal function was gradually recovered and pulmonary hemorrhage completely disappeared by treatment with antihypertensive agents. The authors report a case of malignant hypertension with a rare complication of pulmonary alveolar hemorrhage and speculate that it may be related to vascular injuries at the alveolar capillary level caused by malignant hypertension. Copyright (C) 2000 S. Karger AG, Basel.

DOI： 10.1159/000013558

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

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

We report here a case of severe acute pancreatitis associated with systemic AA amyloidosis in a 69-year-old rheumatoid arthritis (RA) patient. AA amyloid deposition was detected on the walls of small pancreatic arteries and arterioles. The acute pancreatitis was resistant to various interventions, and acute necrotizing pancreatitis and multiple organ failure developed. Although AA amyloidosis in RA patients is rarely complicated with acute pancreatitis, acute pancreatitis in such cases could be severe and intractable and might result in a fatal outcome.

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

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER PHYSIOLOGICAL SOC

Extracellular matrix (ECM) proteins, their integrin receptors, and matrix metalloproteinases (MMPs), the ECM-degrading enzymes, are believed to be involved in various biological processes, including embryogenesis. In the present study, we investigated the role of membrane type MMP, MT-1-MMP, an activator pro-MMP-2, in metanephric development. Also, its relationship with MMP-2 and its inhibitor, TIMP-2, was studied. Since mRNAs of MT-1-MMP and MMP-2 are respectively expressed in the ureteric bud epithelia and mesenchyme, they are ideally suited for juxtacrine/paracrine interactions during renal development. Northern blot analyses revealed a single similar to 4.5-kb mRNA transcript of MT-1-MMP, and its expression was developmentally regulated. Inclusion of MT-1-MMP antisense oligodeoxynucleotide (ODN) in the culture media induced dysmorphogenetic changes in the embryonic metanephros. MMP-2 antisense ODN also induced similar changes, but they were relatively less; on the other hand TIMP-2 antisense ODN induced a mild increase in the size of explants. Concomitant exposure of MT-1-MMP and MMP-2 antisense ODNs induced profound alterations in the metanephroi. Treatment of TIMP-2 antisense ODN to metanephroi exposed to MT-1-MMP/MMP-2 antisense notably restored the morphology of the explants. Specificity of the MT-1-MMP antisense ODN was reflected in the selective decrease in its mRNA and protein expression. The MT-1-MMP antisense ODN also resulted in a failure in the activation of pro-MMP-2 to MMP-8. These findings suggest that the trimacromolecular complex of MT-1-MMP:MMP-2:TIMP-2 modulates the organogenesis of the metanephros, conceivably by mediating paracrine/juxtacrine epithelial:mesenchymal interactions.

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

Language：English Publishing type：Research paper (scientific journal) Publisher：NATL ACAD SCIENCES

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein and is expressed in the renal tubular basement membranes. Its role in metanephric development was investigated. TIN-ag cDNA, isolated from the newborn mouse library, had an ORF of 1,425 nucleotides, a putative signal sequence, and an ATP/GTP-binding site. The translated sequence had approximate to 80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA was primarily expressed in the newborn kidney. In. the embryonic metanephros, TIN-ag expression was confined to the distal convolution or pole of the S-shaped body, the segment of the nascent nephron that is the progenitor of renal tubules. Treatment with TIN ag antisense oligodeoxynucleotide induced dysmorphogenesis of the embryonic metanephroi, malformation of the S-shaped body, and a decrease in the tubular population, whereas the glomeruli were unaffected. Treatment also led to a decrease of TIN-Ag mRNA, de novo synthesis of TIN-ag protein, and its antibody reactivity. The mRNA expression of glomerular epithelial protein 1 (a marker for renal podocytes), anti-heparan-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lectin staining of the metanephros were unaffected. The anti-TIN-ag antibody treatment also caused deformation of the S-shaped body and a reduction in the tubular population, whereas the glomeruli were unchanged. The data suggest that the TIN-ag, unlike other basement membrane proteins, selectively regulates tubulogenesis, whereas glomerulogenesis is largely unaffected.

DOI： 10.1073/pnas.96.20.11323

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC

Previously, we reported that the formation of focal adhesion accelerated by accumulation of extracellular matrices may inhibit the angiotensin II-stimulated proliferation of human mesangial cells (HMCs). The process is regulated by p44/42 MAP kinase activity through the mediation of paxillin and GTPase activating proteins. In this report, we investigated the effect of integrin molecules on the angiotensin II-induced p44/42 MAP kinase activation in non-adherent HMCs. The results demonstrated that incubation of cells with both antibody to integrin beta(1) chain (K20) and GRGDS peptide induced integrin clustering, paxillin aggregation, and marked suppression of angiotensin II-induced p44/42 MAP kinase activation. On the other hand, incubation of cells with K20 alone induced integrin clustering without paxillin aggregation and the suppressive effect on angiotensin II-stimulated p44/42 MAP kinase activity. Our results strongly suggest the pivotal role of integrins in the inhibitory effect of focal adhesion on p44/42 MAP kinase activity, the checking system against angiotensin II-induced MAP kinase overactivation. (C) 1999 Academic Press.

DOI： 10.1006/bbrc.1999.1080

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

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL SCIENCE INC

Background. In diabetic and nondiabetic renal diseases, glomerular hyperfiltration is believed to play a central role in the subsequent progression of glomerulosclerosis and interstitial renal scarring. To identify genes involved in the process of hyperfiltration and hypertrophy, a polymerase chain reaction (PCR)-based subtraction method, that is, representational difference analysis of cDNA (cDNA-RDA), was employed.
Methods. Ten-week-old ICR mice were 5/6 nephrectomized and sham operated. After two weeks, mRNAs were isolated from control and remnant kidneys and were subjected to the cDNA-RDA procedure.
Results. We identified 10 known and 9 novel genes. Among 19 clones, 12 clones (8 known and 4 novel) showed 1.5- to 6-fold up-regulation by Northern blot analyses. The remaining seven clones were rarely expressed genes and were barely detected by Northern blot analyses, and their up-regulated expression was confirmed by Southern blot analysis using the PCR-amplified representative amplicons. The known genes included kidney androgen-regulated protein, major urinary protein, lysozyme M, metalloproteinase-3 tissue inhibitor, chaperonin 10, cytochrome oxidase I, epsilon-sarcoglycan, ribosomal protein S3a, G-protein gamma(10) subunit, and splicing factor 9G8. All of the isolated known genes have not been reported to be up-regulated in the nephrectomized mouse kidney and suggest the possible role of androgen action: mitochondrial functions, matrix metabolism, cell-matrix interactions, and intracellular signaling events in the initiation of the progressive renal injury of the remnant kidney. Furthermore, cDNA-RDA facilitates the discovery of novel genes, including two kidney-specific genes.
Conclusions. The isolated known and novel genes may be involved in the pathobiological process of initial hyperfiltration and hypertrophy of remnant kidney.

DOI： 10.1046/j.1523-1755.1999.00561.x

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC

Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for alpha v beta 3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had similar to 88% homology with human fibrillin-2 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an similar to 10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an similar to 350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-alpha v and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial: mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs. (C) 1999 Academic Press.

DOI： 10.1006/dbio.1999.9331

　 PREV - NEXT 　

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26