Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China.
Int J Biol Sci. 2019 Jun 4;15(8):1618-1629. doi: 10.7150/ijbs.33323. eCollection 2019.
Tripartite motif (Trim) 8 is an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is closely involved in innate immunity. However, the function of Trim8 in hepatic ischaemia/reperfusion (I/R) injury remains largely unknown. The aim of this study is to explore the role of Trim8 in hepatic I/R injury. Trim8 gene knockout mice and primary hepatocytes were used to construct hepatic I/R models. The effect of Trim8 on hepatic I/R injury was analysed via pathological and molecular analyses. The results indicated that Trim8 was significantly upregulated in liver of mice subjected to hepatic I/R injury. Trim8 knockout relieved hepatocyte injury triggered by I/R. Silencing of Trim8 expression alleviated hepatic inflammation responses and inhibited apoptosis and . Mechanistically, our study suggests that Trim8 deficiency may elicit hepatic protective effects by inhibiting the activation of transforming growth factor β-activated kinase 1 (TAK1)-p38/JNK signalling pathways. TAK1 was required for Trim8 function in hepatic I/R injury as TAK1 activation abolished Trim8 function . In conclusion, our study demonstrates that Trim8 deficiency plays a protective role in hepatic I/R injury by inhibiting the activation of TAK1-dependent signalling pathways.
三结构域蛋白 8（Trim）8 是一种 E3 泛素连接酶，可与多种底物相互作用并泛素化，并且与先天免疫密切相关。然而，Trim8 在肝缺血/再灌注（I/R）损伤中的作用在很大程度上仍不清楚。本研究旨在探讨 Trim8 在肝 I/R 损伤中的作用。使用 Trim8 基因敲除小鼠和原代肝细胞构建肝 I/R 模型。通过病理和分子分析来分析 Trim8 对肝 I/R 损伤的影响。结果表明，Trim8 在经受肝 I/R 损伤的小鼠肝脏中明显上调。Trim8 敲除减轻了 I/R 引发的肝细胞损伤。Trim8 表达的沉默减轻了肝炎症反应，并抑制了细胞凋亡。机制上，我们的研究表明，Trim8 缺乏可能通过抑制转化生长因子-β激活激酶 1（TAK1）-p38/JNK 信号通路的激活来发挥肝保护作用。TAK1 是 Trim8 在肝 I/R 损伤中发挥作用所必需的，因为 TAK1 的激活消除了 Trim8 的功能。总之，本研究表明，Trim8 缺乏通过抑制 TAK1 依赖性信号通路的激活在肝 I/R 损伤中发挥保护作用。
