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% 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.
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% 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: Zsofia I Kovacs; Saejeong Kim; Neekita Jikaria; Farhan Qureshi; Blerta Milo; Bobbi K Lewis; Michele Bresler; Scott R Burks; Joseph A Frank Journal: Proc Natl Acad Sci U S A Date: 2016-12-19 Impact factor: 11.205
Authors: Ewa Trojan; Joanna Ślusarczyk; Katarzyna Chamera; Katarzyna Kotarska; Katarzyna Głombik; Marta Kubera; Agnieszka Basta-Kaim Journal: Front Pharmacol Date: 2017-11-01 Impact factor: 5.810