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

作者全名："Chen, Qing-song; Shen, Ai; Dai, Jiang-wen; Li, Ting-ting; Huang, Wei-feng; Shi, Kun; Deng, Yi; Pan, Long; Wei, Xu-fu; Wu, Zhong-jun"

作者地址："[Chen, Qing-song; Dai, Jiang-wen; Li, Ting-ting; Huang, Wei-feng; Shi, Kun; Deng, Yi; Pan, Long; Wei, Xu-fu; Wu, Zhong-jun] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing, Peoples R China; [Shen, Ai] Chongqing Univ, Dept Hepatobiliary Pancreat, Canc Hosp, Canc Ctr, Chongqing, Peoples R China; [Deng, Yi] Chongqing Med Univ, Dept Oncol, Yongchuan Hosp, Chongqing, Peoples R China"

通信作者："Wei, XF; Wu, ZJ (corresponding author), Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：LIFE SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000647710200004

JCR分区：Q1

影响因子：6.1

年份：2021

卷号：276

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：IL37; Autophagy; Apoptosis; Ischaemia; reperfusion; AMPK; mTOR; ULK1

摘要："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."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672959, 81703063]; Natural Science Foundation of Chongqing, ChinaNatural Science Foundation of Chongqing [cstc 2018jscx-msybX0133, cstc2018jcyjAX0800, cstc2017jcyjBX0043]; Postgraduate Innovation Project of Chongqing Education Commission, Chongqing, China [CYB19140]; Natural Science Foundation Project of Yongchuan, Chongqing, China [Ycstc 2018nb0201]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (grant NO. 81672959 and 81703063), the Natural Science Foundation of Chongqing, China (grant NO. cstc 2018jscx-msybX0133, cstc2018jcyjAX0800 and cstc2017jcyjBX0043), Postgraduate Innovation Project of Chongqing Education Commission, Chongqing, China (grant NO. CYB19140), and the Natural Science Foundation Project of Yongchuan, Chongqing, China (grant NO. Ycstc 2018nb0201)."