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 mechanismremains 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 thatmiR-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 conditionswasmediated 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.