PMID- 25587068 OWN - NLM STAT- MEDLINE DCOM- 20150911 LR - 20220321 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 26 IP - 7 DP - 2015 Jul TI - MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin Homolog in Renal Ischemia-Reperfusion Injury. PG - 1588-96 LID - 10.1681/ASN.2014050463 [doi] AB - 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. CI - Copyright (c) 2015 by the American Society of Nephrology. FAU - Bhatt, Kirti AU - Bhatt K AD - Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; FAU - Wei, Qingqing AU - Wei Q AD - Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; FAU - Pabla, Navjotsingh AU - Pabla N AD - Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; FAU - Dong, Guie AU - Dong G AD - Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; FAU - Mi, Qing-Sheng AU - Mi QS AD - Departments of Dermatology and Internal Medicine, Henry Ford Health System, Detroit, Michigan; FAU - Liang, Mingyu AU - Liang M AD - Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; FAU - Mei, Changlin AU - Mei C AD - Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China; and. FAU - Dong, Zheng AU - Dong Z AD - 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. LA - eng GR - I01 BX000319/BX/BLRD VA/United States GR - R01 DK058831/DK/NIDDK NIH HHS/United States GR - R01 DK087843/DK/NIDDK NIH HHS/United States GR - R01 HL121233/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150113 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (MicroRNAs) RN - 0 (Microfilament Proteins) RN - 0 (Tensins) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (Pten protein, mouse) SB - IM CIN - J Am Soc Nephrol. 2015 Jul;26(7):1478-80. PMID: 25587069 MH - Analysis of Variance MH - Animals MH - Blotting, Northern MH - Disease Models, Animal MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Kidney Diseases/*physiopathology MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/metabolism MH - Microfilament Proteins/*genetics/metabolism MH - PTEN Phosphohydrolase/*genetics MH - Random Allocation MH - Real-Time Polymerase Chain Reaction/methods MH - Reperfusion Injury/*physiopathology MH - Signal Transduction MH - Tensins MH - Up-Regulation PMC - PMC4483585 OTO - NOTNLM OT - acute renal failure OT - cell death OT - hypoxia OT - ischemia-reperfusion OT - renal injury EDAT- 2015/01/15 06:00 MHDA- 2015/09/12 06:00 PMCR- 2016/07/01 CRDT- 2015/01/15 06:00 PHST- 2014/05/12 00:00 [received] PHST- 2014/09/12 00:00 [accepted] PHST- 2015/01/15 06:00 [entrez] PHST- 2015/01/15 06:00 [pubmed] PHST- 2015/09/12 06:00 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - ASN.2014050463 [pii] AID - 2014050463 [pii] AID - 10.1681/ASN.2014050463 [doi] PST - ppublish SO - J Am Soc Nephrol. 2015 Jul;26(7):1588-96. doi: 10.1681/ASN.2014050463. Epub 2015 Jan 13.