Int J Med Sci 2021; 18(16):3831-3838. doi:10.7150/ijms.52011 This issue

Research Paper

REV-ERBα Agonist GSK4112 attenuates Fas-induced Acute Hepatic Damage in Mice

Ruyue Shao1,2, Yongqiang Yang3, Kerui Fan3, Xicheng Wu3, Rong Jiang4, Li Tang3, Longjiang Li3, Yi Shen3, Gang Liu5✉, Li Zhang3✉

1. Clinical Medical School, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.
2. Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing 401331, China.
3. Department of Pathophysiology, Basic Medical College, Chongqing Medical University, Chongqing 400016, China.
4. Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
5. Department of Emergency, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China.

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Citation:
Shao R, Yang Y, Fan K, Wu X, Jiang R, Tang L, Li L, Shen Y, Liu G, Zhang L. REV-ERBα Agonist GSK4112 attenuates Fas-induced Acute Hepatic Damage in Mice. Int J Med Sci 2021; 18(16):3831-3838. doi:10.7150/ijms.52011. Available from https://www.medsci.org/v18p3831.htm

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Abstract

Graphic abstract

Fas-induced apoptosis is a central mechanism of hepatocyte damage during acute and chronic hepatic disorders. Increasing evidence suggests that circadian clock plays critical roles in the regulation of cell fates. In the present study, the potential significance of REV-ERBα, a core ingredient of circadian clock, in Fas-induced acute liver injury has been investigated. The anti-Fas antibody Jo2 was injected intraperitoneally in mice to induce acute liver injury and the REV-ERBα agonist GSK4112 was administered. The results indicated that treatment of GSK4112 decreased the level of plasma ALT and AST, attenuated the liver histological changes, and promoted the survival rate in Jo2-insulted mice. Treatment with GSK4112 also downregulated the activities of caspase-3 and caspase-8, suppressed hepatocyte apoptosis. In addition, treatment with GSK4112 decreased the level of Fas and enhanced the phosphorylation of Akt. In conclusion, treatment with GSK4112 alleviated Fas-induced apoptotic liver damage in mice, suggesting that REV-ERBα agonist might have potential value in pharmacological intervention of Fas-associated liver injury.

Keywords: Acute hepatic injury, Apoptosis, Fas, REV-ERBα, Circadian clock