HEAT SHOCK PROTEIN 70/NITRIC OXIDE EFFECT ON STRETCHED TUBULAR EPITHELIAL CELLS LINKED TO WT-1 CYTOPROTECTION DURING NEONATAL OBSTRUCTIVE NEPHROPATHY

LUCIANA MAZZEI; DARÍO CUELLO-CARRIÓN; NEIL G. DOCHERTY; WALTER MANUCHA

INTERNATIONAL UROLOGY AND NEPHROLOGY

SPRINGER

Lugar: Berlin; Año: 2017 vol. 49 p. 1875 - 1892

0301-1623

Mechanical stress is key pathogenic driver of apoptosis in the tubular epithelium in obstructive nephropathy. Heat shock protein 70 (Hsp70) and Wilms tumor (WT-1) have been proposed to represent linked downstream effectors of the cytoprotective properties of NO. In present study we sought to evaluate whether the cytoprotective effects of L-arginine in neonatal obstructive nephropathy may be associated with NO dependent increases in WT-1 and Hsp70 expression.Neonatal Wistar-Kyoto rats were submitted to complete unilateral ureteral obstruction (UUO) and treated thereafter with Vehicle, L-NAME or L-arginine by daily gavage for 14 days to block or augment NO levels respectively. Normal rat kidney epithelial cells by (NRK-52E) were exposed to cyclic mechanical stress in vitro in the presence or absence of L-NAME, L-arginine, sodium nitroprusside (SNP), L-arginine + SNP or Larginine/L-NAME. Induction of apoptosis and the mRNA expression of WT-1 and Hsp70 genes were assessed WT-1 and Hsp70 genes expression decreased in the presence of L-NAME and following UUO coincident with increased tubular apoptosis. L-arginine treatment increased NO levels, reduced apoptosis and restored expression levels of WT-1 and Hsp70 to control levels. L-arginine treatment in vitro reduced basal apoptotic rates and prevented apoptosis in response to mechanical strain, an effect enhanced by SNP coincubation.L-NAME increased apoptosis and prevented the anti-apoptotic action of Larginine.L-arginine treatment in experimental neonatal UUO reduces apoptosis coincident with restoration of WT-1 and Hsp70 expression levels and directly inhibits mechanical strain induced apoptosis in an NO dependent manner in vitro. This potentially implicates an NO-Hsp70-WT-1 axis in the cytoprotective effects of L-arginine.