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Hypoxia enhances CXCR4 expression favoring microglia migration via HIF-1alpha activation |
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| Authors: | Wang Xubu Li Caixia Chen Yang Hao Yutong Zhou Wen Chen Chunhai Yu Zhengping |
| Institution: | a Department of Occupational Health, The Third Military Medical University, Chongqing 400038, People’s Republic of China b Department of Gynaecology and Obstetrics, Southwest Hospital, Chongqing, People’s Republic of China c Department of Neurology, The Third Military Medical University, Chongqing, People’s Republic of China |
| Abstract: | 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-1α (SDF-1α) 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-1α (HIF-1α) 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-1α-CXCR4 pathway during microglia migration. |
| Keywords: | Hypoxia Microglia CXCR4 receptor HIF-1α Cell migration |
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