自噬
二甲双胍
车站3
脂肪性肝炎
STAT蛋白
炎症
体内
细胞生物学
生物
癌症研究
药理学
化学
信号转导
免疫学
医学
内分泌学
内科学
脂肪肝
生物化学
细胞凋亡
糖尿病
生物技术
疾病
作者
Yongli Li,Xiangqian Li,Yadong Wang,Chuan Shen,Caiyan Zhao
标识
DOI:10.1016/j.bbrc.2019.03.077
摘要
Autophagy is an intracellular recycling and degradation process for regulating cell survival and drug resistance. Non-alcoholic steatohepatitis (NASH) is becoming a widespread disease in developing countries. However, the role of autophagy in NASH has not yet been fully elucidated. The present study determined that signal transducer and activator of transcription 3 (STAT3), in the inflammation and autophagy regulation, was the key in the progression of NASH. In NASH mouse and cell models, STAT3 mRNA and protein expressions were significantly increased, while the induction of autophagy was radically decreased. Furthermore, the effects of metformin on STAT3 expression level and NASH inflammation were investigated. The current results showed that metformin activated autophagy and decreased the mRNA expressions of inflammatory cytokines, IL-1β, IL-6, and TNF-α via inhibition of the STAT3 mRNA and protein expression. The siRNA targeting STAT3 activated autophagy and inhibited the NASH inflammatory response by reducing the mRNA expressions of the inflammatory cytokines in vivo and in vitro. The correlation between autophagy and inflammation was also explored. Autophagy induced by metformin attenuated the inflammatory response. This phenomenon of inflammation reduction was partially restored by treatment with the autophagy inhibitor 3-methylindole (3-MA). In conclusion, this study demonstrated that metformin alleviated the inflammatory response in the liver and the hepatocyte of the NASH model via STAT3-mediated autophagy induction. This mechanism provides a strategy for targeting the NASH inflammatory response.
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