NITRIC OXIDE EFFECT ON STRETCHED TUBULAR EPITHELIAL CELLS LINKED TO WT-1 CYTOPROTECTION DURING NEONATAL OBSTRUCTIVE NEPHROPATHY

LUCIANA MAZZEI; WALTER MANUCHA; NEIL G. DOCHERTY

Mendoza

Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2016

Sociedad de Biología de Cuyo

A major feature of the injury sustained by the kidney during an obstruction of the urinary tract is a profound induction of apoptosis in the tubular epithelium. In this sense, mechanical stretch is related to renal tubular apoptosis and nitric oxide plays a key role. Furthermore, a decreased nitric oxide (NO) and heat shock protein 70 (Hsp70) expression associated with Wilms tumor (WT-1) gen low expression were shown in obstructed kidneys from neonatal rats. Therefore, we performed the present study to evaluate if NO cytoprotective effects during mechanical stretch injury may be mediated via increases in WT-1 expression linked to Hsp70 dependent pathways. Wistar-Kyoto rats were submitted to complete unilateral ureteral obstruction within 48 h after birth and treated with L-NAME or L-arginine. Also, NRK-52E cells were subjected to mechanical stress. The expressions of Hsp70 and WT-1 were evaluated in order to measure apoptosis induction and to evaluate NO effect. Nephrogenic and cytoprotective gene expression were decreased in obstruction and with the use of L-NAME but remained as controls with L-arginine treatment. The cells with L-arginine showed a reduction in apoptosis even in control cells without stress. L-NAME increased the apoptosis in the groups exposed to mechanical strain but not in control group. We found a cytoprotective role of NO associated to WT-1 expression as well to Hsp70 dependent pathways during conditions involving both mechanical and oxidative stress as well as in neonatal obstructive nephropathy.