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Publication : Hypoxia enhances CXCR4 expression favoring microglia migration via HIF-1alpha activation.

First Author  Wang X Year  2008
Journal  Biochem Biophys Res Commun Volume  371
Issue  2 Pages  283-8
PubMed ID  18435916 Mgi Jnum  J:136264
Mgi Id  MGI:3795807 Doi  10.1016/j.bbrc.2008.04.055
Citation  Wang X, et al. (2008) Hypoxia enhances CXCR4 expression favoring microglia migration via HIF-1alpha activation. Biochem Biophys Res Commun 371(2):283-8
abstractText  Migration toward pathological area is the first critical step in microglia engagement during the central nervous system (CNS) injury, although the molecular mechanisms underlying microglia mobilization have not been fully understood. Here, we report that hypoxia promotes stromal cell-derived factor-1alpha (SDF-1alpha) induced microglia migration by inducing the CXC chemokine receptor 4 (CXCR4) expression. Exposure to hypoxia significantly enhanced CXCR4 expression levels in N9 microglia cell. Then, cell migration induced by SDF-1, a CXCR4-specific ligand, was observed accelerated. Blockade of hypoxia inducible factor-1alpha (HIF-1alpha) activation by inhibitors of phosphoinositide-3-kinase (PI3K)/Akt signaling pathway abrogated both of hypoxia-induced CXCR4 up-regulation and cell-migration acceleration. These results point to a crucial role of Hypoxia-HIF-1alpha-CXCR4 pathway during microglia migration.
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