The Migration of Neural Progenitor Cell Mediated by SDF ‐1 is NF ‐κ B / HIF ‐1α Dependent upon Hypoxia

Summary Aims Stromal cell‐derived factor 1 ( SDF ‐1) is critical for neural progenitor cell ( NPC ) migration after ischemia for nerve repair, but how hypoxic induction of SDF ‐1 is regulated has not been fully addressed. Here, we examined the regulation of SDF ‐1 hypoxic induction by the transcription factors nuclear factor‐κ B ( NF ‐κ B ) and hypoxic inducible factor 1α ( HIF ‐1α) in astrocytes. Methods and Results Stromal cell‐derived factor‐1 in astrocyte‐conditioned medium ( ACM ) collected from hypoxic astrocytes induced a time‐ and dose‐dependent increase in NPC migration using chemotaxis assay. The increase in NPC migration correlated with increased SDF ‐1 production in astrocytes by real‐time PCR and ELISA assays. Astrocytes produced SDF ‐1 time‐dependently upon 3% O 2 treatment, which was associated with increased levels of NF ‐κB and HIF ‐1α using W estern blot analysis. Anti‐ HIF ‐1α compound, 3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzylindazole ( YC ‐1) and NF ‐κB inhibitor pyrrolidine dithiocarbamate ( PDTC ), decreased hypoxic induction of SDF ‐1, and PDTC pretreatment cancelled HIF ‐1α expression as well, thus NPC migration induced by ACM was decreased accordingly. Moreover, lentiviurs si RNA for NF ‐κ B p65 abrogated induction of HIF ‐1α and SDF ‐1 under hypoxia in astrocytes. Conclusions Hypoxic induction of SDF ‐1 is reliant upon NF ‐κ B and HIF ‐1α. There is a cross‐talk between HIF ‐1α and NF ‐κ B , both HIF ‐1α and SDF ‐1 are downstream targets of NF ‐κ B in hypoxia condition.