Eur Rev Med Pharmacol Sci 2018; 22 (22): 7621-7627

DOI: 10.26355/eurrev_201811_16378

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

J. Xu, T.-T. Yu, K. Zhang, M. Li, H.-J. Shi, X.-J. Meng, L.-S. Zhu, L.-K. Zhu

Department of Nephrology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, China. zjgszyyykjk@126.com


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-β1 (TGF-β1)-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 α-SMA (α-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 α-SMA in fibrotic NRK-52E cells. After overexpression of HGF in UUO mice, α-SMA was remarkably downregulated, whereas E-cadherin was significantly upregulated. Further, results also demonstrated that HGF was upregulated and α-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-β1/SMAD signaling pathway.

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To cite this article

J. Xu, T.-T. Yu, K. Zhang, M. Li, H.-J. Shi, X.-J. Meng, L.-S. Zhu, L.-K. Zhu
HGF alleviates renal interstitial fibrosis via inhibiting the TGF-β1/SMAD pathway

Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 22
Pages: 7621-7627
DOI: 10.26355/eurrev_201811_16378