title: Mild hypothermia pretreatment protects hepatocytes against ischemia reperfusion injury via down-regulating miR-122 and IGF-1R/AKT pathway.
abstract: Mild hypothermia has been well known as an effective way to reduce ischemia reperfusion injury (IRI), while the mechanisms are still unclear. More and more evidences have indicated that miRNAs should been involved in the regulation of IRI and expecially some miRNAs have shown temp-responsiveness for temperature variation. Therefore, the role of miR-122 in mild hypothermia pretreatment after IRI was investigated.
  
  
  
  We established a LO2 cell anoxia-reoxygenation injury model to simulate liver IRI. Five groups of differently pretreated L02 cells were studied. ALT, AST and LDH as well as cell viability were measured. Flow cytometric analysis was used to evaluate the apoptosis. The expression of miR-122 was quantified by qRT-PCR. Insulin-like growth factor 1 receptor (IGF-1R), protein kinase B (p-AKT), AKT, forkhead box O3a (p-FOXO3a) and Caspase3 were examined using western blot analysis.
  
  
  
  We found that mild hypothermia pretreatment could reduce the hepatocellular injury and induce a significant down-regulation in miR-122 expression after IRI. However, those effects of protection were attenuated by overexpressed miR-122 blockade. We further demonstrated that down-regulation of miR-122 promoted IGF-1R translation and AKT activity, suppressed FOXO3a activity and Caspase3 expression after mild hypothermia pretreatment, which was abrogated by miR-122 mimic.
  
  
  
  Our data clearly demonstrate that mild hypothermia pretreatment can down-regulate miR-122 to protect hepatocytes against IRI through activation IGF-1R/AKT signaling pathway and inhibit cells apoptosis.
authors.affiliation: Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, PR China; Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, 430071, PR China. Electronic address: yqf_china@163.com.
authors.forename: Qi Fa
authors.initials: QF
authors.lastname: Ye
authors.affiliation: Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China.
authors.forename: Bi Qi
authors.initials: BQ
authors.lastname: Fu
authors.affiliation: Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xia
authors.affiliation: Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Zhong Zhong
authors.initials: ZZ
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Xing Jian
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Yan Feng
authors.initials: YF
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015536:Down-Regulation; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods; D035683:MicroRNAs / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D017526:Receptor, IGF Type 1
keywords: AKT; IGF-1R; Ischemia reperfusion; Mild hypothermia pretreatment; microRNA-122