Ontology highlight
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 ?-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.
SUBMITTER: Chen SY
PROVIDER: S-EPMC7898667 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Chen San-Yang SY Zhang Hua-Peng HP Li Jie J Shi Ji-Hua JH Tang Hong-Wei HW Zhang Yi Y Zhang Jia-Kai JK Wen Pei-Hao PH Wang Zhi-Hui ZH Shi Xiao-Yi XY He Yu-Ting YT Hu Bo-Wen BW Yang Han H Guo Wen-Zhi WZ Zhang Shui-Jun SJ
Hepatology (Baltimore, Md.) 20210206 2
<h4>Background and aims</h4>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.<h4>Approach and results</h4>This study systemically evaluated the putative role of TRIM27/transforming growth factor β-activat ...[more]