MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin Homolog in Renal Ischemia-Reperfusion Injury.
Journal of the American Society of Nephrology : JASN
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.
Medical Subject Headings
Analysis of Variance; Animals; 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