HGF alleviates renal interstitial fibrosis via inhibiting the TGF-β1/SMAD pathway

OBJECTIVE: To study the role of HGF (stem cell growth factor) in renal interstitial fibrosis and to explore its underlying mechanism. MATERIALS AND METHODS: A unilateral ureteral obstruction (UUO) mouse model was first constructed, and kidney samples of mice were then collected. Fibrosis-related indicators in UUO mice kidney were detected by Western blot. The mRNA and protein levels of HGF in UUO mice were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and Western blot, respectively. The HGF overexpression mouse model was established by using UUO mice. For in vitro experiments, fibrosis-related indicators and the expression of HGF were detected in transforming growth factor-beta 1 (TGF-beta 1)-induced NRK-52E cells. Finally, a p-SMAD3 knockdown mouse model was established to confirm whether p-SMAD3 was involved in HGF-regulated renal interstitial fibrosis. RESULTS: The expression levels of HGF and alpha-SMA (alpha-smooth muscle actin) were both significantly increased in UUO mice, while E-cadherin expression was significantly decreased, which were consistent with results of in vitro experiments. Overexpression of HGF remarkably decreased the protein and mRNA levels of alpha-SMA in fibrotic NRK-52E cells. After overexpression of HGF in UUO mice, alpha-SMA was remarkably downregulated, whereas E-cadherin was significantly upregulated. Further, results also demonstrated that HGF was upregulated and alpha-SMA was downregulated after p-SMAD3 knockdown in UUO mice. CONCLUSIONS: HGF is highly expressed during renal interstitial fibrosis, which may suppress renal interstitial fibrosis by inhibiting the TGF-beta 1/SMAD signaling pathway.