Transforming growth factor β1 and renal injury following subtotal nephrectomy in the rat: Role of the renin-angiotensin system

L. L. Wu, A. Cox, C. J. Roe, M. Dziadek, M. E. Cooper, R. E. Gilbert

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Transforming growth factor-β (TGF-β) 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-β1 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 (AT1) 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-β1 gene expression during a 16-week time course. In situ hybridization localized TGF-β1 mRNA to sclerotic glomeruli, areas of tubulointerstitial injury and sites of mononuclear cell infiltration. Administration of the ACE inhibitor ramipril and the AT1 receptor blocker valsartan blunted the increase in TGF-β1 mRNA, and attenuated the structural and functional manifestations of injury. These data suggest an interaction between the intrarenal RAS and TGF-β in the pathogenesis of the glomerular and tubulointerstitial fibrosis that follow a major reduction in renal mass.

Original languageEnglish
Pages (from-to)1553-1567
Number of pages15
JournalKidney International
Issue number5
Publication statusPublished - 1 Jan 1997
Externally publishedYes

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