UMM Logo

Universitas Muhammadiyah Malang


Free Download Journals Directory


Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2010 > Volume 59 Number 2 > Seiji NISHIBAYASHI1)4), Katsuji HATTORI2), Takahiro HIRANO2), Kenji UEHARA2), Yoshimasa NAKANO2), Miki AIHARA2), Yoshihisa YAMADA2), Masahiro MURAGUCHI3), Fusako IWATA3) and Yoshiharu TAKIGUCHI4)

Functional and Structural Changes in End-Stage Kidney Disease due to Glomerulonephritis Induced by the Recombinant α3(IV)NC1 Domain

Seiji NISHIBAYASHI1)4), Katsuji HATTORI2), Takahiro HIRANO2), Kenji UEHARA2), Yoshimasa NAKANO2), Miki AIHARA2), Yoshihisa YAMADA2), Masahiro MURAGUCHI3), Fusako IWATA3) and Yoshiharu TAKIGUCHI4)
1) Quests Research Institute, Otsuka Pharmaceutical Co., Ltd. 2) First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd. 3) Institute of Biomedical Innovation, Otsuka Pharmaceutical Co., Ltd. 4) Department of Clinical pharmacology, Institute of Health Bioscience, The University of Tokushima Graduate School
Abstract :

The aim of this study was to develop and characterize a rat glomerulonephritis model, which progresses to renal fibrosis and renal failure. A single immunization of female WKY rats with more than 10 μg of recombinant α3(IV)NC1 protein caused severe proteinuria followed by progressive increases in plasma creatinine and blood urea nitrogen (BUN) level within 42 days. Sequential histopathological evaluation revealed crescent formation in glomeruli followed by tubular dilation and interstitial fibrosis. Hydroxyproline content and expression of type I collagen and smooth muscle actin genes in the renal cortex increased as renal dysfunction progressed. Furthermore, the TGF-β1 level in the renal cortex also increased. In the evaluation of antinephritic agents in this model, prednisolone and mycophenolate mofetil (MMF) treatment significantly decreased plasma creatinine and BUN, and suppressed renal fibrosis and histological changes involving crescent formation, compared with the vehicle-treated nephritic rats, whereas lisinopril treatment failed to improve renal function and histology. We demonstrated that immunization of female WKY rats with a sufficient dose of recombinant α3(IV)NC1 induces end-stage kidney disease accompanied by renal fibrosis. The relatively short period needed to induce the disease and the high incidence of functional and structural changes were considered a great advantage of this model for clarifying the mechanisms of progressive glomerulonephritis and for evaluating agents used to treat renal failure.

Keywords :
α3 chain of type IV collagen, end-stage renal failure, renal fibrosis

Date Deposited : 21 Jun 2011 13:43

Last Modified : 21 Jun 2011 14:19

Official URL: http://www.jstage.jst.go.jp/browse/expanim/60/1/_contents

Volume 59, Number 2, - 2010

Download:
Full Text Original
Abstract : pdf doc
Home | Peta Situs | Admissions | Student Research | E-Journal
Universitas Muhammadiyah Malang © 2011
Developed by Infokom UMM
Last Update : 13 December 2016 20:46Kumpulan file jurnal