title: Interferon regulatory factor-1 activates autophagy to aggravate hepatic ischemia-reperfusion injury via the P38/P62 pathway in mice.
abstract: Increasing evidence has linked autophagy to a detrimental role in hepatic ischemia- reperfusion (IR) injury (IRI). Here we focus on the role of interferon regulatory factor-1 (IRF-1) in regulating autophagy to aggravate hepatic IRI. We found that IRF-1 was up-regulated during hepatic IRI and was associated with an activation of the autophagic signaling. This increased IRF-1 expression, which was allied with high autophagic activity, amplified liver damage to IR, an effect which was abrogated by IRF-1 depletion. Moreover, IRF-1 contributed to P38 induced autophagic and apoptotic cell death, that can play a key role in liver dysfunction. The levels of P62 mRNA and protein were increased when P38 was activated and decreased when P38 was inhibited by SB203580. We conclude that IRF-1 functioned as a trigger to activate autophagy via P38 activation and that P62 was required for this P38-mediated autophagy. IRF-1 appears to exert a pivotal role in hepatic IRI, by predisposing hepatocytes to activate an autophagic pathway. Such an effect promotes autophagic cell death through the P38/P62 pathway. The identification of this novel pathway, that links expression levels of IRF-1 with autophagy, may provide new insights for the generation of novel protective therapies directed against hepatic IRI.
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin 300192, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin 300192, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Li
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin 300192, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin 300192, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.
authors.forename: Jindan
authors.initials: J
authors.lastname: He
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin 300192, China.|Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.|Oriental Organ Transplant Center, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Oriental Organ Transplant Center, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Yu
authors.affiliation: Oriental Organ Transplant Center, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.|Oriental Organ Transplant Center, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Zilin
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Tianjin Nankai Hospital, Tianjin 300100, China.
authors.forename: Ximo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Immunology and Inflammation, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300071, China.|Oriental Organ Transplant Center, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Hongyin
authors.initials: H
authors.lastname: Du
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071456:Sequestosome-1 Protein / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D050856:Interferon Regulatory Factor-1; D000071456:Sequestosome-1 Protein; D048051:p38 Mitogen-Activated Protein Kinases