p38丝裂原活化蛋白激酶
细胞凋亡
细胞生物学
信号转导
炎症
激酶
癌症研究
生物
蛋白激酶A
免疫学
生物化学
作者
Sanyang Chen,Huapeng Zhang,Jie Li,Jihua Shi,Hongwei Tang,Yi Zhang,Jiakai Zhang,Peihao Wen,Zhi‐Hui Wang,Xiaoyi Shi,Yu‐Ting He,Bowen Hu,Han Yang,Wenzhi Guo,Shuijun Zhang
出处
期刊:Hepatology
[Wiley]
日期:2020-04-28
卷期号:73 (2): 738-758
被引量:47
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI