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Transforming growth factor beta 1 and renal injury following subtotal nephrectomy in the rat: Role of the renin-angiotensin system
Author(s): Wu LL, Cox A, Roe CJ, Dziadek M, Cooper ME, Gilbert RE
Source: KIDNEY INTERNATIONAL    Volume: 51    Issue: 5    Pages: 1553-1567    Published: MAY 1997  
Times Cited: 143     References: 76     
Abstract: Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS) have both been implicated in the pathogenesis of chronic renal disease. The present experiment investigated the chronology of TGF-beta 1 gene expression following subtotal nephrectomy (STNx) in the rat and the effect of blocking the RAS by angiotensin converting enzyme (ACE) inhibition or by angiotensin II receptor (AT(1)) antagonism. Rats that had undergone subtotal nephrectomy developed hypertension, proteinuria, renal impairment, glomerulosclerosis, tubulointerstitial fibrosis and mononuclear cell infiltration. These changes were associated with a 2.5-fold increase in TGF-beta 1 gene expression during a 16-week time course. In situ hybridization localized TGF-beta 1 mRNA to sclerotic glomeruli, areas of tubulointerstitial injury and sites of mononuclear cell infiltration. Administration of the ACE inhibitor ramipril and the AT(1) receptor blocker valsartan blunted the increase in TGF-beta 1 mRNA, and attenuated the structural and functional manifestations of injury. These data suggest an interaction between the intrarenal RAS and TGF-beta in the pathogenesis of the glomerular and tubulointerstitial fibrosis that follow a major reduction in renal mass.
Document Type: Proceedings Paper
Language: English
Addresses:
1. AUSTIN & REPATRIAT MED CTR, DEPT MED, ENDOCRINOL UNIT, HEIDELBERG, VIC 3084 AUSTRALIA
2. UNIV MELBOURNE, DEPT ANAT & CELL BIOL, MELBOURNE, VIC AUSTRALIA
Publisher: BLACKWELL SCIENCE INC, 350 MAIN ST, MALDEN, MA 02148
Subject Category: Urology & Nephrology
IDS Number: WX906
ISSN: 0085-2538
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