Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 513, Issue 1, Pages 64-72Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.03.077
Keywords
Metformin; Inflammation; Methionine and choline-deficient (MCD); diet or medium; Non-alcoholic steatohepatitis; STAT3; Autophagy
Categories
Funding
- Key Project of Heibei Natural Science Fund [H2016206550]
Ask authors/readers for more resources
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-1 beta, IL-6, and TNF-alpha 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. (C) 2019 Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available