| First Author | Sun P | Year | 2018 |
| Journal | Hepatology | Volume | 68 |
| Issue | 6 | Pages | 2359-2375 |
| PubMed ID | 29742804 | Mgi Jnum | J:288150 |
| Mgi Id | MGI:6430355 | Doi | 10.1002/hep.30086 |
| Citation | Sun P, et al. (2018) Monocyte Chemoattractant Protein-Induced Protein 1 Targets Hypoxia-Inducible Factor 1alpha to Protect Against Hepatic Ischemia/Reperfusion Injury. Hepatology 68(6):2359-2375 |
| abstractText | 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 1alpha (HIF-1alpha) expression by deubiquitinating HIF-1alpha. Notably, the HIF-1alpha inhibitor reversed the protective effect of MCPIP1, whereas the HIF-1alpha activator compensated for the detrimental effect of MCPIP1 deficiency. Thus, we identified the MCPIP1-HIF-1alpha axis as a critical pathway that may be a good target for intervention in hepatic I/R injury. (Hepatology 2018; 00:000-000). |
