title: Retinoic acid receptor α promotes autophagy to alleviate liver ischemia and reperfusion injury.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Chen Zhong, Li-Yong Pu, Jian-Hua Rao, Xue-Hao Wang, Key Laboratory of Living Donor Liver Transplantation of Chinese Ministry of Health, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Chen Zhong, Li-Yong Pu, Jian-Hua Rao, Xue-Hao Wang, Key Laboratory of Living Donor Liver Transplantation of Chinese Ministry of Health, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Pu
authors.affiliation: Chen Zhong, Li-Yong Pu, Jian-Hua Rao, Xue-Hao Wang, Key Laboratory of Living Donor Liver Transplantation of Chinese Ministry of Health, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Fang
authors.affiliation: Chen Zhong, Li-Yong Pu, Jian-Hua Rao, Xue-Hao Wang, Key Laboratory of Living Donor Liver Transplantation of Chinese Ministry of Health, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Chen Zhong, Li-Yong Pu, Jian-Hua Rao, Xue-Hao Wang, Key Laboratory of Living Donor Liver Transplantation of Chinese Ministry of Health, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Rao
authors.affiliation: Chen Zhong, Li-Yong Pu, Jian-Hua Rao, Xue-Hao Wang, Key Laboratory of Living Donor Liver Transplantation of Chinese Ministry of Health, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Xue-Hao
authors.initials: XH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D019610:Cytoprotection; D003984:Dibenzazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D003984:Dibenzazepines; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C467200:Foxo1 protein, mouse; C104183:LE 540; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt
keywords: Autophagy; Foxo1; Foxo3a; Ischemia/reperfusion; Retinoic acid receptor α