title: The migration of neural progenitor cell mediated by SDF-1 is NF-κB/HIF-1α dependent upon hypoxia.
abstract: OBJECTIVE
  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.
  
  
  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 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.
authors: Department of Emergency, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors: Wen
authors: W
authors: Yin
authors: Lei
authors: L
authors: Ma
authors: Jun
authors: J
authors: Zhang
authors: Kun
authors: K
authors: Huang
authors: Qi
authors: Q
authors: Yang
authors: Yan-Yan
authors: YY
authors: Guo
authors: Shui-Bing
authors: SB
authors: Liu
authors: Yong-Hong
authors: YH
authors: Liu
authors: Yu-Mei
authors: YM
authors: Wu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D054377:Chemokine CXCL12; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B