MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin Homolog in Renal Ischemia-Reperfusion Injury. J Am Soc Nephrol 2015 Jul;26(7):1588-96
Date
01/15/2015Pubmed ID
25587068Pubmed Central ID
PMC4483585DOI
10.1681/ASN.2014050463Scopus ID
2-s2.0-84934756768 (requires institutional sign-in at Scopus site) 90 CitationsAbstract
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.
Author List
Bhatt K, Wei Q, Pabla N, Dong G, Mi QS, Liang M, Mei C, Dong ZMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Blotting, Northern
Disease Models, Animal
Hypoxia-Inducible Factor 1, alpha Subunit
Kidney Diseases
Mice
Mice, Inbred C57BL
MicroRNAs
Microfilament Proteins
PTEN Phosphohydrolase
Random Allocation
Real-Time Polymerase Chain Reaction
Reperfusion Injury
Signal Transduction
Tensins
Up-Regulation