Resveratrol inhibited hepatocyte apoptosis and alleviated liver fibrosis through miR-190a-5p /HGF axis

Abstract

BackgroundHepatocyte apoptosis plays an important role in the progression of liver fibrosis. Overexpression of HGF (Hepatocyte growth factor) can reduce hepatocyte apoptosis and alleviate liver fibrosis. Our study aims to investigate whether resveratrol (Res) can alleviate liver fibrosis through miR-190a-5p /HGF axis. MethodsThe TGF-β1 (transforming growth factor-β1)-induced primary hepatocyte model in vitro and CCl4-induced liver fibrosis model in vivo were established. Hepatocyte apoptosis was determined by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. HE (hematoxylin and eosin) staining and Sirius red staining were performed to observe the pathological changes of the liver tissues. Western blotting was used to determine the expression of apoptosis-associated proteins and HGF. Quantitative Real-time PCR (QRT-PCR) was used to quantify miR-190a-5p expression. The dual-luciferase reporter assay was performed to verify the targeting relationship between miR-190a-5p and HGF. ResultsHepatocyte apoptosis and miR-190a-5p expression level were increased in TGF-β1-induced cell models in vitro while the results were reversed after treatment with Res. Besides, miR-190a-5p negatively regulated HGF expression, and miR-190a-5p regulated hepatocyte apoptosis by targeting HGF. Res reduced the apoptosis of hepatocytes and the effect was achieved by decreasing the expression levels of miR-190a-5p and increasing HGF expression in vitro. Moreover, experiments in vivo verified that Res reduced apoptosis of the hepatocytes reduced AST, and ALT levels, as well as raised Albumin levels in the serum. Apart from that, Res decreased the expression ofmiR-190a-5p and increased HGF levels at the same time, and further reduced liver fibrosis. ConclusionIn summary, our study indicated that Res could inhibit the up-regulation of miR-190a-5p caused by CCl4 or TGF-β1. And then the decreased miR-190a-5p could further lessen the hepatocyte apoptosis by increasing HGF levels and finally relieving liver fibrosis.