Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12381
Peer-review started: March 13, 2015
First decision: June 2, 2015
Revised: June 19, 2015
Accepted: August 25, 2015
Article in press: August 25, 2015
Published online: November 21, 2015
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 H2O2in 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.
Core tip: To investigate the role of autophagy and the relationship between all-trans retinoic acid (ATRA) and autophagy in liver ischemia and reperfusion (IR) injury. We found that ATRA pretreatment alleviated liver IR injury by inducing autophagy and it may involves retinoic acid receptor α (RARα) activity. To clarify the mechanism of RARα, we used LE540 to inhibit RARα during reactive oxygen species-inducing cell damage in vitro. Our data showed that RARα activation enhanced Foxo3a and p-Akt expression except Foxo1. The Foxo3a/p-Akt/Foxo1 pathway has previously been proven to promote autophagy. Hence, we conclude that ATRA activates RARα to reduce liver IR injury by regulating the Foxo3a/p-Akt/Foxo1 pathway to promote autophagy.