Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Neurosci Lett. 2012 Mar 28;513(1):42-6. doi: 10.1016/j.neulet.2012.02.004. Epub 2012 Feb 10.
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.
在灰质中,已知脑内皮细胞为邻近的神经元等细胞提供营养支持。然而,脑内皮细胞向白质细胞发出的信号仍有待阐明。在这里,我们发现脑内皮细胞分泌的血管内皮生长因子(VEGF-A)促进少突胶质前体细胞(OPC)的迁移而不是增殖。原代培养的 OPC 取自新生大鼠皮质,用脑内皮细胞的条件培养基处理可增加 OPC 的增殖和迁移。重要的是,与 Flk-1(VEGF 受体 2)的中和抗体共同处理可抑制 OPC 运动,但不影响 OPC 增殖。Western blot 和流式细胞术分析证实,我们培养的脑内皮细胞产生 VEGF-A,我们培养的 OPC 表达 Flk-1。总之,我们目前的数据表明,脑内皮细胞对少突胶质谱系细胞具有支持作用,而 VEGF-A 可能参与内皮细胞-OPC 细胞间信号传递。这种现象对白质稳态可能很重要。