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Monocyte Chemoattractant Protein‐Induced Protein 1 Targets Hypoxia‐Inducible Factor 1α to Protect Against Hepatic Ischemia/Reperfusion Injury
Author(s) -
Sun Peng,
Lu YueXin,
Cheng Daqing,
Zhang Kuo,
Zheng Jilin,
Liu Yupeng,
Wang Xiaozhan,
Yuan YuFeng,
Tang YiDa
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30086
Subject(s) - inflammation , monocyte , downregulation and upregulation , liver injury , hepatocyte , reperfusion injury , hypoxia (environmental) , chemotaxis , activator (genetics) , immunology , ischemia , medicine , chemistry , pharmacology , receptor , biochemistry , gene , in vitro , organic chemistry , oxygen
Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein‐induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte‐specific Mcpip1 gene knockout and transgenic mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration. A mechanistic study revealed that MCPIP1 interacted with and maintained hypoxia‐inducible factor 1α (HIF‐1α) expression by deubiquitinating HIF‐1α. Notably, the HIF‐1α inhibitor reversed the protective effect of MCPIP1, whereas the HIF‐1α activator compensated for the detrimental effect of MCPIP1 deficiency. Thus, we identified the MCPIP1–HIF‐1α axis as a critical pathway that may be a good target for intervention in hepatic I/R injury. (H epatology 2018; 00:000‐000).