Inhibition of EGFR attenuates fibrosis and stellate cell activation in diet-induced model of nonalcoholic fatty liver disease

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Liang, Dandan¹  Chen, Hongjin^1,2  Zhao, Leping²  Zhang, Wenxin¹  Hu, Jie¹  Liu, Zhiguo¹  Zhong, Peng¹  Wang, Wei³  Wang, Jingying¹  Liang, Guang^1,2 

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Yueqing Hosp, Dept Pharm, Wenzhou 325000, Peoples R China

[3] Qingdao Univ, Sch Med, Qingdao 266071, Shandong, Peoples R China

关键词: Liver fibrosis;    EGFR;    Oxidative stress;    Stellate cell;    NAFLD;   

DOI  :  10.1016/j.bbadis.2017.10.016

来源: Elsevier

【 摘 要 】

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD begins with steatosis and advances to nonalcoholic steatohepatitis (NASH) and cirrhosis. The molecular mechanisms involved in NAFLD progression are not understood. Based on recent studies showing dysregulation of epidermal growth factor receptor (EGFR) in animal models of liver injury, we sought to determine if inhibition of EGFR mitigates liver fibrosis and HSC activation in NAFLD. We utilized the high fat diet (HFD)-induced murine model of liver injury to study the role of EGFR in NAFLD. The lipid accumulation, oxidative stress, hepatic stellate cell (HSC) activation and matrix deposition were examined in the liver tissues. We also evaluated the EGFR signaling pathway, ROS activation and pro-fibrogenic phenotype in oxidized low density lipoproteins (ox-LDL) challenged cultured HSCs. We demonstrate that EGFR was phosphorylated in liver tissues of HFD murine model of NAFLD. Inhibition of EGFR prevented diet -induced lipid accumulation, oxidative stress, and HSC activation and matrix deposition. In cultured HSCs, we show that ox-LDL caused rapid activation of the EGFR signaling pathway and induce the production of reactive oxygen species. EGFR also mediated HSC activation and promoted a pro-fibrogenic phenotype. In conclusion, our data demonstrate that EGFR plays an important role in NAFLD and is an attractive target for NAFLD therapy.

【 授权许可】

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