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Monocyte Chemoattractant Protein-Induced Protein 1 Targets Hypoxia-Inducible Factor 1α to Protect Against Hepatic Ischemia/Reperfusion Injury
- Source :
- Hepatology (Baltimore, Md.). 68(6)
- Publication Year :
- 2018
-
Abstract
- 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. (Hepatology 2018; 00:000-000).
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Male
Programmed cell death
Primary Cell Culture
Inflammation
Apoptosis
Pharmacology
03 medical and health sciences
Mice
0302 clinical medicine
Ribonucleases
Downregulation and upregulation
medicine
Animals
Humans
Hepatology
Activator (genetics)
business.industry
Monocyte
Liver Diseases
medicine.disease
Hypoxia-Inducible Factor 1, alpha Subunit
Liver Regeneration
030104 developmental biology
medicine.anatomical_structure
Hypoxia-inducible factors
Liver
030220 oncology & carcinogenesis
Case-Control Studies
Reperfusion Injury
Hepatocytes
medicine.symptom
business
Reperfusion injury
Transcription Factors
Subjects
Details
- ISSN :
- 15273350
- Volume :
- 68
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Hepatology (Baltimore, Md.)
- Accession number :
- edsair.doi.dedup.....a06336a7d4177ca0b61d4d1d3f0ffa4f