Netrin-1 attenuates the progression of renal dysfunction by inhibiting peritubular capillary loss and hypoxia in 5/6 nephrectomized rats

Abstract

Background/Aims: The aim of this study was to investigate the effect of netrin-1 on peritubular capillary (PTC) loss and hypoxia in 5/6 nephrectomized (Nx) rats. Methods: Male Sprague-Dawley rats were divided into three groups (n = 10 rats/group): sham-operated rats treated with control adenovirus; 5/6 Nx rats treated with control adenovirus; and 5/6 Nx rats treated with recombinant adenovirus mediated netrin-1 gene (Ad-netrin-1) therapy. Rats were killed 12 weeks after surgery. Blood urea nitrogen (BUN), serum creatinine (Scr) and 24-h urinary albumin excretion rates were measured. Pathological changes in renal tissues were analyzed histologically. The concentration of netrin-1, CD34, and hypoxia-inducible factor-1α (HIF-1α) were analyzed by immunohistochemistry, Western blotting and real-time PCR. Results: Renal function and histopathological damage were significantly improved in Adnetrin- 1 treated 5/6 Nx rats, compared with rats treated with the control adenovirus in the 5/6 Nx group. Furthermore, Ad-netrin-1 treatment induced a significant increase in renal PTC density, accompanied by a significant decrease in HIF-1α expression. Conclusion: Adenovirus mediated netrin-1 treatment attenuates PTC damage, relieves tissues hypoxia and improves renal function, thus alleviating renal pathological changes and interstitial fibrosis in 5/6 Nx rats. © 2012 S. Karger AG, Basel.