title: Vascular endothelial growth factor regulates the migration of oligodendrocyte precursor cells.
abstract: Originally identified as an angiogenic factor, vascular endothelial growth factor (VEGF-A) is now known to play multiple roles in the CNS, including the direct regulation of neuronal and astrocytic functions. Here, we ask whether VEGF-A can also have a novel role in white matter by modulating oligodendrocyte precursor cells (OPCs). OPCs were cultured from rat neonatal cortex. Expression of VEGF-receptor2/KDR/Flk-1 was confirmed with Western blot and immunostaining. VEGF-A did not affect proliferation or differentiation in OPC cultures, but VEGF-A promoted OPC migration in a concentration-dependent manner. Consistent with this migration phenotype, VEGF-A-treated OPCs showed reorganization of actin cytoskeleton in leading-edge processes. VEGF-A-induced migration and actin reorganization were inhibited by an anti-Flk-1 receptor-blocking antibody. Mechanistically, VEGF-A induced binding of focal adhesion kinase (FAK) with paxillin. The FAK inhibitor PF573228 reduced VEGF-A-induced OPC migration. VEGF-A signaling also evoked a transient rise in reactive oxygen species (ROS), and OPC migration was increased when antioxidants were removed from the culture media. Our findings demonstrate that VEGF-A can induce OPC migration via an ROS- and FAK-dependent mechanism, and suggest a novel role for VEGF-A in white-matter maintenance and homeostasis.
authors.affiliation: Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Loc-Duyen D
authors.initials: LD
authors.lastname: Pham
authors.forename: Angel T
authors.initials: AT
authors.lastname: Som
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lee
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Guo
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D008297:Male; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D051419:Paxillin / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000199:Actins; D000941:Antigens; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005732:Gangliosides; D051419:Paxillin; D011509:Proteoglycans; D015363:Quinolones; D013450:Sulfones; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099216:Chondroitin Sulfate Proteoglycan 4; C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; C062875:ganglioside A2B5