Study of molecular mechanisms responsible for renal injury in neonatal obstructive nephrophaty

LUCIANA MAZZEI; ISABEL MERCEDES GARCÍA; WALTER MANUCHA

Centro de Congresos y Exposiciones de Mendoza

Congreso; XXVIII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2010

Sociedad de Biología de Cuyo

Congenital obstructive nephropathy is characterised by tubular cell apoptosis and tubulointerstitial fibrosis and is a major cause of renal failure in the neonate. In the neonatal rat, only 10% of the nephrogenic programme is complete and hence the rat offers a model in which to test the efficacy of novel therapies for this pathology. Statins such as rosuvastatin (Ros), inhibit the rate-limiting step of the cholesterol biosynthetic pathway. Statins prevent the activation of apoptotic and fibrotic processes in renal cells in vitro and renal fibrosis in vivo. The present study examined whether Ros could protect against neonatal obstructive nephropathy in the rat associated to preservation of the nephrogenesis key modulators expression. Two-day old rats underwent unilateral ureteral obstruction (UUO) or sham surgery (Control), were randomised to receive oral Ros (10mg/kg/day) or vehicle for 14 days. On day 14, renal cortex was processed for determination of tubular dilatation, apoptosis, tubulointerstitial fibrosis and the mRNA expression of TNF-a, TGF-b1, WT1, Snail, BMP-7 and E-cadherin. UUO significantly increased tubular apoptosis, tubular dilatation and tubulointerstitial fibrosis, coupled to increases in the expression of TNF-a and TGF-b1 mRNA. Ros treatment during UUO markedly protected against these changes. Ros treatment was associated with the preservation of renal expression of WT1, Snail, BMP-7 and E-cadherin.  Conclusion: Ros protects against the generation of obstructive nephropathy in the neonatal rat. The protective effects of Ros were sufficient to preserve a normal profile of expression for a number of markers of nephrogenesis