title: MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression.
abstract: Hepatic ischemia/reperfusion injury (IRI) represents an important clinical problem as related to liver resection or transplantation. However, the potential mechanism underlying hepatic IRI remains obscure. Recent evidence has indicated that microRNAs (miRNAs) participate in various hepatic pathophysiological processes via regulating autophagy. This relationship between MicroRNA-17 (miR-17) and hepatic autophagy prompted us to examine the role and potential mechanisms of miR-17 regulating autophagy in hepatic IRI. MiR-17 levels were significantly up-regulated after hepatic ischemia/reperfusion (IR), and the number of autophagosomes increased in response to IR. These results demonstrate that miR-17 could promote hepatic IRI as revealed by reductions in cell viability in vitro. The expression of microtubule-associated protein 1 light B II (LC3BII) was gradually up-regulated and peaked at 24 hours following reperfusion, a time point that was also associated with maximal miR-17 levels. Overexpression of miR-17 diminished signal transductions and activation of transcription-3 (Stat3) and phosphorylated Stat3 (p-Stat3) levels, an effect which promoted autophagy in response to IRI. However, low-level expressions of miR-17 were associated with increased Stat3 and p-Stat3 levels and decreased autophagy. In conclusion, high levels of miR-17 expression can function to up-regulate autophagy to aggravate hepatic IRI by suppressing Stat3 expression. Liver Transplantation 22 1697-1709 2016 AASLD.
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.|Department of General Surgery, People's Hospital of Jiaozuo City, Jiaozua, China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Li
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Wang
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Jindan
authors.initials: J
authors.lastname: He
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Zhang
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: First Central Clinical College of Tianjin Medical University, Tianjin, China.|Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin, China.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D000071182:Autophagosomes / Q000502:physiology*; D001343:Autophagy / Q000235:genetics*; D002460:Cell Line; D002470:Cell Survival; D004195:Disease Models, Animal; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C480860:Map1lc3b protein, mouse; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C543614:Mirn17 microRNA, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse