Tripartite Motif 8 Deficiency Relieves Hepatic Ischaemia/reperfusion Injury via TAK1-dependent Signalling Pathways

• Published in: International journal of biological sciences Vol. 15; no. 8; pp. 1618 - 1629
• Main Authors: Tao, Qiu, Tianyu, Wang, Jiangqiao, Zhou, Zhongbao, Chen, Xiaoxiong, Ma, Long, Zhang, Jilin, Zou
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2019; Ivyspring International Publisher
• Subjects: Activation; Alanine Transaminase - genetics; Alanine Transaminase - metabolism; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Aspartate Aminotransferases - genetics; Aspartate Aminotransferases - metabolism; Blotting, Western; Cells, Cultured; Growth factors; Hepatocytes; Immunity; In Situ Nick-End Labeling; In vivo methods and tests; Inflammation - genetics; Inflammation - metabolism; Injuries; Injury analysis; Innate immunity; Ischemia; Kinases; Liver; Male; Mice; Mice, Knockout; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Polymerase Chain Reaction; Reperfusion; Research Paper; Signal transduction; Signal Transduction - genetics; Signal Transduction - physiology; Signaling; Substrates; TAK1 protein; Transforming growth factor; Transforming growth factor-b; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination - genetics; Ubiquitination - physiology; Ubiquitination; Inflammation; Trim8; Ischaemia/reperfusion; Hepatology; Apoptosis
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.33323

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.