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Therapeutic Effect of HGF on NASH Mice Through HGF/c-Met and JAK2-STAT3 Signalling Pathway

Ning Li, Zhangfeng Dou, Jinchun Liu, Bao Chai, Yue Li, Xiuqin An, Peiling Chu, Xiaolan Zhang

Abstract

Introduction and aim. Hepatocyte growth factor (HGF) has been shown to ameliorate liver inflammation and fibrosis; however, the mechanism underlying its effects in non-alcoholic steatohepatitis (NASH) is unclear. This study aimed to analyse the relationship between the JAK2-STAT3 signalling pathway and the ameliorating effect of HGF on NASH. Material and methods. Mice were fed a high-fat diet (HFD) for 16 weeks, and then plasma and hepatic tissues were collected. Histological and clinical chemistry assays were performed to assess liver disease. The mRNA and protein levels of JAK2, STAT3, and c-Met were assessed by real-time PCR and western blotting, respectively. Results. Serum ALT, AST, and TG levels were increased in NASH mice. Histological analysis showed different degrees of steatosis, inflammatory infiltrates, and fibrosis in HFD animals. Exogenous administration of recombinant human (rh) HGF via the tail vein for 14 days markedly decreased ALT and AST to levels lower than those in the control group. Compared with the levels in HFD mice, c-Met, p-c-Met, JAK2, p-JAK2, and p-STAT3 levels were increased in mice that were administered HGF (P < 0.05). Furthermore, silencing of HGF or blocking of its receptor c-Met affected JAK2 and STAT3 protein phosphorylation. Conclusions. Excess HGF highly probable improved NASH liver function. Combined with its ligand, c-Met, HGF may promote the phosphorylation of JAK2-STAT3 and inhibit inflammation in NASH. Therefore, it may be potentially useful treatment for NASH.

Key words. Non-alcoholic steatohepatitis., Hepatocyte growth factor., HGF/c-Met., JAK2-STAT3 signalling pathway.

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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