Abstract: Objective To explore if HIF-1α can regulate PPARγ2 in mimic hypoxia by CoCl2. Methods By realtime PCR and Western Blot, we examined the mRNA and protein levels of PPARγ2 and HIF-1α. Dual luciferase reporter system analysis and chromatin immunoprecipitation (ChIP) analysis were performed to explore if HIF-1α could regulate PPARγ2 directly. Results The expression analyses revealed coincident trends that the mRNA and protein levels of PPARγ2 and HIF-1α increase in an induction time-dependent manner. By transient transfection experiments, we demonstrated that the overexpresstion of HIF-1α resulted in the up-regulation of PPARγ expression while knockdown of HIF-1α resulted in the down-regulation of PPARγ expression. Dual luciferase reporter system analysis revealed that HIF-1α could active the PPARγ2 in a HIF-1α dose-dependent manner. ChIP analysis and site-directed mutagenesis of the PPARγ2 promoter confirmed the binding of HIF-1α to PPARγ promoter. Conclusion Our results suggested that PPARγ takes a part in hypoxia adaptation in a HIF-1α-dependent manner under mimic hypoxia by CoCl2.

Key words: hypoxia, CoCl2, peroxisome proliferator-activated receptor γ2(PPARγ2), HIF-1α，HRE