Tripartite Motif‐Containing 27 Attenuates Liver Ischemia/Reperfusion Injury by Suppressing Transforming Growth Factor β–Activated Kinase 1 (TAK1) by TAK1 Binding Protein 2/3 Degradation. Issue 2 (6th February 2021)

• Record Type: Journal Article
• Authors: Chen, San‐Yang; Zhang, Hua‐Peng; Li, Jie; Shi, Ji‐Hua; Tang, Hong‐Wei; Zhang, Yi; Zhang, Jia‐Kai; Wen, Pei‐Hao; Wang, Zhi‐Hui; Shi, Xiao‐Yi; He, Yu‐Ting; Hu, Bo‐Wen; Yang, Han; Guo, Wen‐Zhi; Zhang, Shui‐Jun
• Is Part Of: Hepatology. Volume 73:Issue 2(2021)
• Page Start: 738
• Page End: 758
• Publication Date: 2021-02-06
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.31295
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : Background and Aims: Hepatic ischemia‐reperfusion (I/R) injury, which mainly involves inflammatory responses and apoptosis, is a common cause of organ dysfunction in liver transplantation (LT). As a critical mediator of inflammation and apoptosis in various cell types, the role of tripartite motif‐containing (TRIM) 27 in hepatic I/R injury remains worthy of study. Approach and Results: This study systemically evaluated the putative role of TRIM27/transforming growth factor β–activated kinase 1 (TAK1)/JNK (c‐Jun N‐terminal kinase)/p38 signaling in hepatic I/R injury. TRIM27 expression was significantly down‐regulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Subsequently, using global Trim27 knockout mice ( Trim27‐ KO mice) and hepatocyte‐specific Trim27 transgenic mice ( Trim27‐ HTG mice), TRIM27 functions to ameliorate liver damage, reduce the inflammatory response, and prevent cell apoptosis. In parallel in vitro studies, activating TRIM27 also prevented H/R‐induced hepatocyte inflammation and apoptosis. Mechanistically, TRIM27 constitutively interacted with the critical components, TAK1 and TAK1 binding protein 2/3 (TAB2/3), and promoted the degradation of TAB2/3, leading to inactivation of TAK1 and the subsequent suppression of downstream JNK/p38 signaling. Conclusions: TRIM27 is a key regulator of hepatic I/R injury by mediating the degradation of TAB2/3 and suppression of downstream TAK1‐JNK/p38 signaling. TRIM27 may be a promising approach to protect the liver against I/R‐mediated hepatocellular damage in transplant recipients.