The migration of neural progenitor cell mediated by SDF-1 is NF-κB/HIF-1α dependent upon hypoxia

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-κB (NF-κB) 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% O₂ treatment, which was associated with increased levels of NF-κB and HIF-1α using Western 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 siRNA for NF-κB p65 abrogated induction of HIF-1α and SDF-1 under hypoxia in astrocytes. Conclusions: Hypoxic induction of SDF-1 is reliant upon NF-κB and HIF-1α. There is a cross-talk between HIF-1α and NF-κB, both HIF-1α and SDF-1 are downstream targets of NF-κB in hypoxia condition.