Vascular endothelial growth factor regulates the migration of oligodendrocyte precursor cells.
Vascular endothelial growth factor regulates the migration of oligodendrocyte precursor cells.
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DOI：
10.1523/jneurosci.1944-11.2011
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发表时间：
2011-07-20
期刊：
影响因子：
--
通讯作者：
Arai K
中科院分区：
文献类型：
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作者：
Hayakawa K;Pham LD;Som AT;Lee BJ;Guo S;Lo EH;Arai K
血管内皮生长因子（VEGF-A）最初被鉴定为血管生成因子，现在已知在中枢神经系统中起多种作用，包括直接调节神经元和星形胶质细胞功能。在这里，我们询问VEGF-A是否还可以通过调节少突胶质细胞前体细胞（OPC）来在白质中起新颖的作用。从大鼠新生儿皮层培养OPC。通过蛋白质印迹和免疫染色证实了VEGF-topeptor2/kdr/flk-1的表达。 VEGF-A不影响OPC培养物中的增殖或分化。但是VEGF-A以浓度依赖性方式促进了OPC迁移。与这种迁移表型一致，经过VEGF-A处理的OPC显示在领先过程中肌动蛋白细胞骨架的重组。 VEGF-A诱导的迁移和肌动蛋白的重组被抗FLK-1受体阻断抗体抑制。从机械上讲，VEGF-A诱导FAK与帕西林的结合。 FAK抑制剂PF573228降低了VEGF-A诱导的OPC迁移。 VEGF-A信号传导还引起了活性氧（ROS）的短暂上升，当从培养基中去除抗氧化剂时，OPC迁移增加。我们的发现表明，VEGF-A可以通过ROS和FAK依赖性机制诱导OPC迁移，并提出了VEGF-A在白质维持和稳态中的新作用。
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 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.