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J Am Soc Nephrol. 2015 Jul;26(7):1588-96. doi: 10.1681/ASN.2014050463. Epub 2015 Jan 13.

MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin Homolog in Renal Ischemia-Reperfusion Injury.

Author information

1
Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia;
2
Departments of Dermatology and Internal Medicine, Henry Ford Health System, Detroit, Michigan;
3
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
4
Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China; and.
5
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.

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.

KEYWORDS:

acute renal failure; cell death; hypoxia; ischemia-reperfusion; renal injury

PMID:
25587068
PMCID:
PMC4483585
DOI:
10.1681/ASN.2014050463
[Indexed for MEDLINE]
Free PMC Article

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