title: MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin Homolog in Renal Ischemia-Reperfusion Injury.
abstract: Ischemia-reperfusion injury contributes to tissue damage and organ failure in clinical settings, but the underlying mechanism remains elusive and effective therapies are still lacking. Here, we identified microRNA 687 (miR-687) as a key regulator and therapeutic target in renal ischemia-reperfusion injury. We show that miR-687 is markedly upregulated in the kidney during renal ischemia-reperfusion in mice and in cultured kidney cells during hypoxia. MiR-687 induction under these conditions was mediated by hypoxia-inducible factor-1 (HIF-1). Upon induction in vitro, miR-687 repressed the expression of phosphatase and tensin homolog (PTEN) and facilitated cell cycle progression and apoptosis. Blockade of miR-687 preserved PTEN expression and attenuated cell cycle activation and renal apoptosis, resulting in protection against kidney injury in mice. Collectively, these results unveil a novel HIF-1/miR-687/PTEN signaling pathway in ischemia-reperfusion injury that may be targeted for therapy.
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia;
authors.forename: Kirti
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia;
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia;
authors.forename: Navjotsingh
authors.initials: N
authors.lastname: Pabla
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia;
authors.forename: Guie
authors.initials: G
authors.lastname: Dong
authors.affiliation: Departments of Dermatology and Internal Medicine, Henry Ford Health System, Detroit, Michigan;
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China; and.
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China zdong@gru.edu.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007674:Kidney Diseases / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction; D000070876:Tensins; D015854:Up-Regulation
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D008840:Microfilament Proteins; D000070876:Tensins; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: acute renal failure; cell death; hypoxia; ischemia-reperfusion; renal injury