Aim: To study the role of autophagy and the relationship between retinoic acid receptor α (RARα) and autophagy in liver ischemia and reperfusion (IR) injury.
Methods: All-trans retinoic acid (ATRA) was administered to mice for two weeks before operation. Reverse transcription-polymerase chain reaction and Western blot were used to detect the expression levels of related factors. To demonstrate the role of RARα, LE540, a RARα inhibitor, was used to treat hepatocytes injured by H2O2 in vitro.
Results: ATRA pretreatment noticeably diminished levels of serum alanine aminotransferase and aspartate aminotransferase as well as the degree of histopathological changes. Apoptosis was also inhibited, whereas autophagy was promoted. In vitro, RARα was inhibited by LE540, which resulted in decreased autophagy and increased apoptosis. Similarly, the expression of Foxo3a and p-Akt was downregulated, but Foxo1 expression was upregulated.
Conclusion: This research provides evidence that ATRA can protect the liver from IR injury by promoting autophagy, which is dependent on Foxo3/p-Akt/Foxo1 signaling.
Keywords: Autophagy; Foxo1; Foxo3a; Ischemia/reperfusion; Retinoic acid receptor α.