| First Author | Lin Y | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 529 |
| Issue | 4 | Pages | 916-921 |
| PubMed ID | 32819599 | Mgi Jnum | J:302397 |
| Mgi Id | MGI:6508246 | Doi | 10.1016/j.bbrc.2020.06.152 |
| Citation | Lin Y, et al. (2020) Rev-erbalpha regulates hepatic ischemia-reperfusion injury in mice. Biochem Biophys Res Commun 529(4):916-921 |
| abstractText | Hepatic ischemia-reperfusion (I/R) injury is a complex pathophysiological process that often times occurs in liver transplantation, hepatectomy, and ischemic shock. Aberrant activation of inflammatory responses has been implicated in hepatic I/R injury. In this study, we aimed to investigate the role of circadian clock gene Rev-erbalpha (a well-known regulator of inflammation) in hepatic I/R injury. We first showed that Rev-erbalpha ablation sensitized mice to hepatic I/R injury as evidenced by higher levels of plasma alanine aminotransferase and aspartate aminotransferase, an increased histological score, as well as enhanced hepatic myeloperoxidase activity in Rev-erbalpha(-/-) mice. More severe hepatic I/R injury in Rev-erbalpha(-/-) mice was accompanied by higher expression of pro-inflammatory cytokines, exacerbated activation of Nlrp3 inflammasome, and more extensive infiltration of inflammatory cells. Moreover, pharmacological activation of Rev-erbalpha by SR9009 significantly alleviated the hepatic damage and inflammatory responses. In addition, I/R operation started at ZT18 (corresponding to low Rev-erbalpha expression) caused more severe liver damage and inflammatory responses in wild-type mice as compared to operation started at ZT6 (corresponding to high Rev-erbalpha expression), supporting a protective effect of Rev-erbalpha on hepatic I/R injury. Collectively, Rev-erbalpha protects hepatic I/R injury probably via repression of inflammatory responses, and targeting Rev-erbalpha may be a promising approach for management of hepatic I/R injury. |
