1. Academic Validation
  2. IL37 overexpression inhibits autophagy and apoptosis induced by hepatic ischemia reperfusion injury via modulating AMPK/mTOR/ULLK1 signalling pathways

IL37 overexpression inhibits autophagy and apoptosis induced by hepatic ischemia reperfusion injury via modulating AMPK/mTOR/ULLK1 signalling pathways

  • Life Sci. 2021 Jul 1;276:119424. doi: 10.1016/j.lfs.2021.119424.
Qing-Song Chen 1 Ai Shen 2 Jiang-Wen Dai 1 Ting-Ting Li 1 Wei-Feng Huang 1 Kun Shi 1 Yi Deng 3 Long Pan 1 Xu-Fu Wei 4 Zhong-Jun Wu 5
Affiliations

Affiliations

  • 1 Department of hepatobiliary surgery, the first affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of hepatobiliary pancreatic Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
  • 3 Department of hepatobiliary surgery, the first affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Department of hepatobiliary surgery, the first affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: xwei@hospital.cqmu.edu.cn.
  • 5 Department of hepatobiliary surgery, the first affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: wzjtcy@126.com.
Abstract

Aim: To investigate the potential role of IL37 in hepatic ischemia reperfusion injury and its underlying molecular mechanism.

Methods: C57BL/6 mouse and hepatocytes were used to establish the hepatic ischemia reperfusion (IR) and the hypoxia reoxygenation (HR) injury model in vivo and in vitro, separately. Total extraction of tissue and cell protein expressions of LC3B, Beclin1, p62, cleaved caspase3, caspase3, Bax, bcl2, AMPK, mTOR, ULK1 were detected by western blot. IL37 mRNA and protein level were detected by RT-qPCR and western blot. ALT and AST serum level were measured by microplate readers. H&E staining was used to assess the tissue sections. Autophagy was measured by TEM and confocal laser microscopy. Apoptosis in tissue and cell were detected by TUNEL staining.

Results: Autophagy was aberrantly activated by H2R6 and I1R12. Both exogenous IL37 and endogenous IL37 exerted protective effects on hepatocytes by affecting both autophagy-related proteins, specifically, by suppressing LC3B II and Beclin1 expression and increasing p62 levels and apoptosis-related proteins specifically, by inhibiting cleaved caspase3 and Bax expression and increasing Bcl2 expression during HR. Furthermore, endogenous IL37 inactivated AMPK and ULK1 phosphorylation and promoted mTOR phosphorylation in hepatocytes. Furthermore, in vivo experiments, serum liver Enzyme measurements, TUNEL assays, and histological assessments, as well as other typical evaluations, showed the protective effect of IL37 overexpression in mice.

Conclusion: Endogenous and exogenous IL37 were found to ameliorate hepatic ischemia reperfusion injury by inhibiting excessive Autophagy and Apoptosis, these effects may be connected with the modulation of AMPK/mTOR/ULK1 signalling complex.

Keywords

AMPK/mTOR/ULK1; Apoptosis; Autophagy; IL37; Ischaemia/reperfusion.

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