Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling

• Published in: Frontiers in immunology Vol. 11; p. 506275
• Main Authors: Jiangqiao, Zhou, Tianyu, Wang, Zhongbao, Chen, Long, Zhang, Jilin, Zou, Xiaoxiong, Ma, Tao, Qiu
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29-09-2020
• Subjects: Animals; Immunology; ischaemic/reperfusion injury; liver; Liver - immunology; Liver - pathology; Liver Diseases - genetics; Liver Diseases - immunology; Liver Diseases - pathology; Liver Diseases - prevention & control; Male; MAP Kinase Kinase Kinases - genetics; MAP Kinase Kinase Kinases - immunology; MAP Kinase Signaling System - genetics; MAP Kinase Signaling System - immunology; Mice; Reperfusion Injury - genetics; Reperfusion Injury - immunology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; TAK1; Ubiquitin Thiolesterase - genetics; Ubiquitin Thiolesterase - immunology; ubiquitination; USP10; TAK1; ischaemic/reperfusion injury; USP10; liver; ubiquitination
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.506275

Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury
and
. Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor β-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function
. In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.