biostudies-literatureUnknown7(34)Fang YProlyl hydroxylase domain protein 2 (PHD2) is a key oxygen sensor, setting low steady-state level of hypoxia-inducible factor-α (HIF-α). Here, we showed that treatment of cobalt chloride (CoCl2), a hypoxia mimic, in HK-2 tubular epithelial cells induced PHD2 and HIF-1/2α expression as well as cell apoptosis and autophagy activation. Three methyladenine (3-MA), the autophagy inhibitor, blocked autophagy and protected HK-2 cells from CoCl2. Significantly, siRNA knockdown of PHD2 also protected HK-2 cells from CoCl2,possibly via increasing HIF-1α expression. Reversely, HIF-1α siRNA knockdown almost abolished cytoprotection by PHD2 siRNA in CoCl2-treated HK-2 cells. In vivo, pretreatment with a PHD inhibitor L-mimosine remarkably attenuated mice renal ischemia-reperfusion injuries. MolecularlyOncotarget54317-54328https://www.ebi.ac.uk/biostudies/studies/S-EPMC5342344biostudies-literatureProlyl hydroxylase 2 (PHD2) inhibition protects human renal epithelial cells and mice kidney from hypoxia injury.PMC5342344Fang YDing XZhang HZhong YfalseProlyl hydroxylase 2 (PHD2) inhibition protects human renal epithelial cells and mice kidney from hypoxia injury.Prolyl hydroxylase domain protein 2 (PHD2) is a key oxygen sensor, setting low steady-state level of hypoxia-inducible factor-α (HIF-α). Here, we showed that treatment of cobalt chloride (CoCl2), a hypoxia mimic, in HK-2 tubular epithelial cells induced PHD2 and HIF-1/2α expression as well as cell apoptosis and autophagy activation. Three methyladenine (3-MA), the autophagy inhibitor, blocked autophagy and protected HK-2 cells from CoCl2. Significantly, siRNA knockdown of PHD2 also protected HK-2 cells from CoCl2,possibly via increasing HIF-1α expression. Reversely, HIF-1α siRNA knockdown almost abolished cytoprotection by PHD2 siRNA in CoCl2-treated HK-2 cells. In vivo, pretreatment with a PHD inhibitor L-mimosine remarkably attenuated mice renal ischemia-reperfusion injuries. Molecularly2016-01-01T00:00:00Z2016 Aug2025-04-19T19:44:56.639Z2019-03-27T02:38:09ZS-EPMC53423442752787110.18632/oncotarget.11104