Hepatocyte Growth Factor Inhibits Renal Angiotensin II Expression in 5/6 Nephrectomized Rats

Angiotensin II (Ang II) contributes to renal dysfunction, while hepatocyte growth factor (HGF) protects against renal dysfunction. However, the relationship between Ang II and HGF in chronic kidney disease (CKD) remains unknown. This study aimed to investigate the effect of HGF on Ang II expression in CKD. A rat model of CKD was established using female Wistar rats subjected to 5/6 nephrectomy (5/6 Nx). HGF was overexpressed in rat renal tissues using PCI-neo-HGF. Immunohistochemical staining and western blot analysis of renal Ang II expression were performed in 5/6 Nx rats treated with vehicle (negative control), Lotensin (positive control), or HGF for different periods of time (before 5/6 Nx, 5 and 9 weeks after 5/6 Nx). Compared with the 0-week group (before 5/6 Nx group), the protein expression of Ang II was significantly induced in rat renal tissues at 5 and 9 weeks after 5/6 Nx (p<0.05), suggesting the possible involvement of Ang II in 5/6 Nx-induced CKD. Importantly, HGF treatment for 5 or 9 weeks markedly inhibited renal Ang II expression and greatly improved the renal morphology in 5/6 Nx rats, compared with the vehicle-treated group (p<0.05). The effects of HGF on renal Ang II expression and renal morphology were similar to those of Lotensin, suggesting that HGF may protect against 5/6 Nx-induced CKD through downregulating Ang II. HGF is a novel regulator of Ang II expression and plays a protective role in 5/6 Nx-induced CKD.