The Migration of Neural Progenitor Cell Mediated by SDF-1 is NF-κ B/ 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-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% 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 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. [ABSTRACT FROM AUTHOR]