Caveolin-1 linked to eNOS/Hsp70 interaction on rosuvastatin protection against fibrosis in neonatal obstructive nephropathy

GARCÍA IM; MAZZEI LUCIANA; ALTAMIRANO L; MANUCHA W

San Juan

Congreso; 2da reunión Conjunta Sociedades de Biología República Argentina; 2011

Sociedades de Biología de la República Argentina

Statins restore endothelial nitric oxide (NO) levels by up-regulating endothelial NO synthase (eNOS). Caveolin-1/eNOS interaction is essential for NO levels. Here, we evaluated whether caveolin-1 associated with eNOS/Hsp70 interaction are involved in the rosuvastatin (Ros) tubulointerstitial fibrosis protection effect during neonatal unilateral ureteral obstruction (UUO). Neonatal rats (n=5) subjected to UUO within two days of birth and controls were treated daily with vehicle or Ros (10 mg/kg/day) by oral gavage for 14 days. After UUO, morphometric evaluation of interstitial fibrosis showed increased interstitial volume with reduced NO level, increased caveolin-1, as well as downregulation eNOS and heat shock protein 70 (Hsp70) expression. Conversely, Ros treatment attenuated the fibrotic response linked to high NO availability, decreased caveolin-1, and marked upregulation of eNOS and Hsp70. Coimmunoprecipitation have shown decreased caveolin-1/eNOS as well as increased Hsp70/eNOS interaction, after Ros treatment. A dose dependent effect of rosuvastatin on decreased caveolin-1 expression was shown. In conclusion, our data of increased NO availability, involving interaction of upregulated eNOS/Hsp70 and downregulated caveolin-1 may contribute to the protection against tubulointerstitial fibrosis injury, afforded by rosuvastatin in neonatal early kidney obstruction.