TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK gamma translocation

作者全名："Yang, Hang; Huang, Zuotian; Luo, Yunhai; Lei, Dengliang; Yan, Ping; Shen, Ai; Liu, Wenbin; Li, Dewei; Wu, Zhongjun"

作者地址："[Yang, Hang; Luo, Yunhai; Lei, Dengliang; Yan, Ping; Wu, Zhongjun] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Huang, Zuotian; Shen, Ai; Liu, Wenbin; Li, Dewei] Chongqing Univ, Dept Hepatobiliary Pancreat Tumor Ctr, Canc Hosp, Chongqing, Peoples R China; [Yan, Ping] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, CAS Key Lab Infect & Immun,Univ Chinese Acad Sci, Beijing, Peoples R China"

通信作者："Wu, ZJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China.; Li, DW (通讯作者)，Chongqing Univ, Dept Hepatobiliary Pancreat Tumor Ctr, Canc Hosp, Chongqing, Peoples R China."

来源：MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000984691900001

JCR分区：Q1

影响因子：6

年份：2023

卷号：29

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：TRIM37; Liver ischemia/reperfusion injury; TRAF6; IKK gamma; Inflammation

摘要："Background Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes associated with various liver surgeries. However, there is still a lack of strategies to protect against hepatic I/R injury because of the unknown underlying mechanism. The present study aimed to identify a potential strategy and provide a fundamental experimental basis for treating hepatic I/R injury. Method A classic 70% ischemia/reperfusion injury was established. Immunoprecipitation was used to identify direct interactions between proteins. The expression of proteins from different subcellular localizations was detected by Western blotting. Cell translocation was directly observed by immunofluorescence. HE, TUNEL and ELISA were performed for function tests. Result We report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through the reinforcement of IKK-induced inflammation following dual patterns. Mechanistically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), inducing K63 ubiquitination and eventually leading to the phosphorylation of IKK gamma. TRIM37 enhances the translocation of IKK gamma, a regulatory subunit of the IKK complex, from the nucleus to the cytoplasm, thereby stabilizing the cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK rescued the function of TRIM37 in vivo and in vitro. Conclusion Collectively, the present study discloses some potential function of TRIM37 in hepatic I/R injury. Targeting TRIM37 might be potential for treatment against hepatic I/R injury.Targeting TRIM37 might be a potential treatment strategy against hepatic I/R injury."

基金机构：Chongqing Research Performance Incentive and Guidance Project [cstc2022jxjl120032]; Chongqing Shapingba District Decision consulting and Management innovation project guiding plan project [Jcd202297]; National Natural Science Foundation of China [82170666]

基金资助正文："This study was supported by Chongqing Research Performance Incentive and Guidance Project (cstc2022jxjl120032), Chongqing Shapingba District Decision consulting and Management innovation project guiding plan project (Jcd202297), and the National Natural Science Foundation of China (No. 82170666)."