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Cerebral endothelial derived vascular endothelial growth factor promotes the migration but not the proliferation of oligodendrocyte precursor cells in vitro
Authors:Kazuhide Hayakawa  Ji Hae Seo  Loc-Duyen D. Pham  Nobukazu Miyamoto  Angel T. Som  Shuzhen Guo  Kyu-Won Kim  Eng H. Lo  Ken Arai
Affiliation:1. Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, USA;2. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, USA;3. NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea;4. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Republic of Korea
Abstract:In gray matter, cerebral endothelium is known to provide trophic support for neighboring cells such as neurons. However, signaling from cerebral endothelium to white matter cells remains to be elucidated. Here, we show that vascular endothelial growth factor (VEGF-A) secreted from cerebral endothelial cells promotes the migration but not the proliferation of oligodendrocyte precursor cells (OPCs). Cultured OPCs were obtained from newborn rat cortex, and treatment with conditioned culture media of cerebral endothelial cells increased the OPC proliferation and migration. Importantly, co-treatment with anti-neutralizing antibody for Flk-1 (VEGF-receptor2) inhibited OPC movement but did not affect OPC propagation. Western blot and flow cytometry analyses confirmed that our cultured cerebral endothelial cells produced VEGF-A and our cultured OPCs expressed Flk-1. Taken together, our current data suggest that cerebral endothelium is supportive for oligodendrocyte lineage cells and VEGF-A may participate in the endothelium–OPC cell–cell signaling. This phenomenon may be important for white matter homeostasis.
Keywords:Oligodendrocyte precursor cell   Vascular endothelial growth factor   Migration   Proliferation   Cerebral endothelial cell   Neurovascular unit   Oligovascular niche   White matter
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