Angiotensin‐converting enzyme inhibition attenuates renal platelet‐derived growth factor gene expression and cell proliferation in subtotal nephrectomy

Abstract

SUMMARY:Cell proliferation, matrix accumulation and cell infiltration are characteristic features of progressive glomerulosclerosis and tubulointerstitial fibrosis. Platelet‐derived growth factor (PDGF), a cytokine which has proliferative, prosclerotic and chemokine properties, has been shown to be upregulated in the rat remnant kidney model. Inhibition of the renin–angiotensin system by angiotensin‐converting enzyme (ACE) inhibitors has a beneficial effect on renal function and morphology, but the effect of ACE inhibition on PDGF gene expression and PDGF‐mediated cellular proliferation in subtotal nephrectomy has not been studied in detail. Twelve rats were subtotally nephrectomized (STNx) and received either the ACE inhibitor perindopril or a placebo for 12 weeks. Five sham‐operated rats served as controls. Subtotal nephrectomy was associated with hypertension, proteinuria, elevated plasma creatinine and increased kidney weight. After 12 weeks, PDGF B‐chain mRNA was significantly upregulated in the glomeruli and tubulointerstitium of subtotally nephrectomized rats. ACE inhibition attenuated PDGF mRNA expression in association with a reduction in tubular and glomerular proliferation, as assessed by staining for proliferating cell nuclear antigen. In the context of the known in vitro and in vivo effects of PDGF, it is postulated that the renoprotective action of ACE inhibitors may be partially related to PDGF‐mediated antiproliferative mechanisms.