Angiotensin-converting enzyme inhibition attenuates proteinuria and renal TGF-β1 mRNA expression in rats with chronic renal disease

Evidence suggests that transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine, induces renal extracellular matrix production and glomerular hypertrophy, The aim of the present study was to investigate the effect of captopril on the expression of TGF-beta 1 mRNA in a rat model of chronic renal failure: five-sixths nephrectomy, Chronic renal disease was induced by removal of the right kidney and ligation of three blood vessels supplying the left kidney, Sham-operated animals were used as controls, RNA was extracted from the viable remnant kidney of rats 1 day and 1 and 2 weeks following five-sixths nephrectomy and from the kidneys of rats who underwent sham sugery, TGF-beta 1 mRNA was induced within 24 h of partial nephrectomy, similar to that reported for early-onset genes, Subsequently, TGF-beta 1 mRNA expression continued to increase over the next 2-4 weeks, The upregulation of TGF-beta 1 correlated with the degree of proteinuria, Both the increase in TGF-beta 1 mRNA and proteinuria were abrogated by captopril treatment, In addition, no change in expression of ALK-5 or type II TGF-beta receptors following five-sixths nephrectomy was observed, These data suggest that captopril may protect against development of glomerulosclerosis and proteinuria by reducing TGF-beta 1 expression and hence matrix production.