miR-210 Protects Renal Cell Against Hypoxia-induced Apoptosis by Targeting HIF-1 Alpha

The kidney is vulnerable to hypoxia-induced injury. One of the mechanisms underlying this phenomenon is cell apoptosis triggered by hypoxia-inducible factor-1-alpha (HIF-1 alpha) activation. MicroRNA-210 (miR-210) is known to be induced by HIF-1 alpha and can regulate various pathological processes, but its role in hypoxic kidney injury remains unclear. Here, in both rat systemic hypoxia and local kidney hypoxia models, we found miR-210 levels were upregulated significantly in injured kidney, especially in renal tubular cells. A similar increase was observed in hypoxia-treated human renal tubular HK-2 cells. We also verified that miR-210 can directly suppress HIF-1 alpha expression by targeting the 3 ' untranslated region of HIF-1 alpha mRNA in HK-2 cells in severe hypoxia. Accordingly, miR-210 overexpression caused significant inhibition of the HIF-1 alpha pathway and attenuated apoptosis caused by hypoxia, while miR-210 knockdown exerted the opposite effect. Taken together, our findings verify that miR-210 is involved in the molecular response in hypoxic kidney lesions in vivo and attenuates hypoxia-induced renal tubular cell apoptosis by targeting HIF-1 alpha directly and suppressing HIF-1 alpha pathway activation in vitro.