WT-1 linked to nitric oxide bioavaibility can reverse the VDR/AT1 expression after unilateral ureteral obstruction.

LUCIANA MAZZEI; LAUTARO AVOGADRO; ISABEL MERCEDES GARCÍA; WALTER MANUCHA

Mendoza

Otro; XXXI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2013

Sociedad de Biología de Cuyo

Experimental and clinical evidence indicate that vitamin D deficiency (characterized by dysfunction of tubular epithelial cells and/or loss of renal parenchyma) and angiotensin II (Ang II) up-regulation play a pivotal role in the progression of renal disease associated with obstructive nephropathy. In addition, wilms tumor 1 (WT-1), a key regulator of mesenchymal-epithelial transformation, is downregulated during congenital obstructive nephropathy; and also, there is a functional interaction between WT-1 and vitamin D receptor (VDR)/AT1 expression. Of great interest, nitric oxide (NO) bioavailability associated with heat shock protein 70 (Hsp70) interaction may modulate WT-1 expression, preventing obstruction-induced cell death during neonatal unilateral ureteral obstruction (UUO). Therefore, the goal of this study was to determine if WT-1 linked to nitric oxide bioavaibility, can reverse the VDR/AT1 expression after UUO. Neonatal rats submitted to experimental UUO were treated with either vehicle or NO modulators for 14 days. Decreased NO and Hsp70/VDR expression associated with WT-1 low expression was shown in UUO. Fibrosis and Apoptosis was induced and it was associated with an increased AT1 expression. Conversely, Hsp70/VDR upregulation and an increased WT-1 expression, with less fibrotic/apoptotic response, were observed in the cortex of obstructed kidneys of NO modulators-treated rats. NO also regulated Hsp70 and WT-1 mRNA expression in MDCK cells. Finally, in vivo experiments with NO modulators support our hypothesis that WT-1 linked to NO bioavaibility can reverse the VDR/AT1 expression after UUO.