| First Author | Yan B | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 11 | Pages | e0239119 |
| PubMed ID | 33137133 | Mgi Jnum | J:296973 |
| Mgi Id | MGI:6471518 | Doi | 10.1371/journal.pone.0239119 |
| Citation | Yan B, et al. (2020) Interferon Regulatory Factor-1 (IRF1) activates autophagy to promote liver ischemia/reperfusion injury by inhibiting beta-catenin in mice. PLoS One 15(11):e0239119 |
| abstractText | Autophagy is an important factor in liver ischemia-reperfusion injury. In the current study we investigate the function of interferon regulatory factor-1 (IRF1) in regulating autophagy to promote hepatic ischemia reperfusion injury (IR). The high expression of IRF1 during hepatic IR exhibited increased liver damage and was associated with activation of autophagy shown by Western blot markers, as well as immunofluorescent staining for autophagosomes. These effects were diminished by IRF1 deficiency in IRF1 knock out (KO) mice. Moreover, the autophagy inhibitor 3-MA decreased IR-induced liver necrosis and markedly abrogated the rise in liver injury tests (AST/ALT). beta-catenin expression decreased during liver IR and was increased in the IRF1 KO mice. Immunoprecipitation assay showed the binding between IRF1 and beta-catenin. Overexpression of IRF1 induced autophagy and also inhibited the expression of beta-catenin. beta-catenin inhibitor increased autophagy while beta-catenin agonist suppressed autophagy in primary mouse hepatocytes. These results indicate that IRF1 induced autophagy aggravates hepatic IR injury in part by inhibiting beta-catenin and suggests that targeting IRF1 may be an effective strategy in reducing hepatic IR injury. |
