Hypoxia enhances CXCR4 expression favoring microglia migration via HIF-1alpha activation.
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.
Wang
Xubu
X
Department of Occupational Health, The Third Military Medical University, Chongqing 400038, People's Republic of China.
Li
Caixia
C
Chen
Yang
Y
Hao
Yutong
Y
Zhou
Wen
W
Chen
Chunhai
C
Yu
Zhengping
Z
D000693:Anaerobiosis; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D054377:Chemokine CXCL12; D003035:Cobalt; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019718:Receptors, CXCR4; C514936:CXCR4 protein, mouse; C497443:Hif1a protein, mouse; C018021:cobaltous chloride