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  2. Interleukin 10 inhibits oxidative stress-induced autophagosome formation in hepatic stellate cells by activating the mTOR-STAT3 pathway

Interleukin 10 inhibits oxidative stress-induced autophagosome formation in hepatic stellate cells by activating the mTOR-STAT3 pathway

  • Exp Cell Res. 2022 Feb 15;411(2):113001. doi: 10.1016/j.yexcr.2021.113001.
Jiabing Chen 1 Qilan Guo 1 Qingduo Chen 1 Yizhen Chen 1 Dongmei Chen 2 Zhixin Chen 1 Xiaozhong Wang 3 Yuehong Huang 4
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, 29#Xinquan Road, Gulou District, Fuzhou, 350001, Fujian, China.
  • 2 Department of Clinical Nutrition. Fujian Medical University Union Hospital, 29#Xinquan Road, Gulou District, Fuzhou, 350001, Fujian, China.
  • 3 Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, 29#Xinquan Road, Gulou District, Fuzhou, 350001, Fujian, China. Electronic address: drwangxz@163.com.
  • 4 Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, 29#Xinquan Road, Gulou District, Fuzhou, 350001, Fujian, China. Electronic address: huangyh0391@fjmu.edu.cn.
Abstract

Autophagy is involved in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Previous studies have shown that interleukin 10 (IL-10) has a marked therapeutic effect against liver fibrosis. However, few studies have evaluated the effect of IL-10 on Autophagy in HSCs and fibrotic livers. The aim of this study was to assess the effect of IL-10 on the Autophagy of HSCs in vitro and in vivo and then to explore the underlying pathway. In vitro, The results revealed that IL-10 had inhibitory effects on hydrogen peroxide (H2O2)-induced Autophagy, as evidenced by the decreased LC3II/I ratio and Beclin1 expression, increased p62 expression, reduced numbers of autophagosomes, and blocked Autophagy initiation in HSCs. Mechanistically, IL-10 significantly promoted the phosphorylation of the signal transducer and activator of transcription 3(STAT3) and mammalian target of rapamycin (mTOR), leading to the activation of STAT3 and mTOR, which in turn inhibited Autophagy. In vivo, the increased expression of IL-10 in fibrotic livers inhibited significantly liver fibrosis and decreased the autophagic activity in fibrotic livers and HSCs. Overall, our results indicate that IL-10 suppressed H2O2-induced Autophagy in HSCs by activating the STAT3-mTOR signaling pathway. Present study provides a new theoretical basis for the anti-fibrotic effects of IL-10.

Keywords

Autophagosome; Hepatic stellate cells; Interleukin 10; Signaling pathway.

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