Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
复制标题
DOI：
10.1073/pnas.182296499
复制
发表时间：
2002-09-03
影响因子：
11.1
通讯作者：
Greenberg, DA
中科院分区：
文献类型：
--
作者：
Jin, KL;Zhu, YH;Greenberg, DA
血管内皮生长因子（VEGF）是一种具有神经营养和神经保护作用的血管生成蛋白。由于VEGF促进血管内皮细胞的增殖，我们研究了它也刺激小鼠大脑皮层培养物和成年大鼠大脑中神经元前体细胞增殖的可能性。VEGF（>10 ng/ml）刺激5-溴-2 '-脱氧尿苷（BrdUrd）掺入表达未成熟神经元标记蛋白的细胞中，并使培养物中的细胞数量增加20- 30%。BrdUrd标记的培养细胞表达VEGFR 2/Flk-1，但不表达VEGFR 1/Flt-1受体，VEGF的作用可被VEGFR 2/Flk-1受体酪氨酸激酶抑制剂SU 1498阻断。脑室注射VEGF可增加海马齿状回（DG）脑室下区（SVZ）和颗粒下区（SGZ）细胞的BrdUrd标记，其中VEGFR 2/Flk-1与未成熟神经元标记物doublecortin（Dcx）共定位。在施用VEGF后BrdUrd标记的增加是由细胞增殖的增加引起的，而不是细胞死亡的减少，因为VEGF没有减少SVZ或SGZ中的半胱天冬酶-3切割。在体内VEGF处理后用BrdUrd标记的细胞包括未成熟和成熟的神经元、星形胶质细胞和内皮细胞。这些发现暗示血管生成因子VEGF在神经发生以及。
Vascular endothelia I growth factor (VEGF) is an angiogenic protein with neurotrophic and neuroprotective effects. Because VEGF promotes the proliferation of vascular endothelial cells, we examined the possibility that it also stimulates the proliferation of neuronal precursors in murine cerebral cortical cultures and in adult rat brain in vivo. VEGF (>10 ng/ml) stimulated 5-bromo-2'-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20-30%. Cultured cells labeled by BrdUrd expressed VEGFR2/Flk-1, but not VEGFR1/Flt-1 receptors, and the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. Intracerebroventricular administration of VEGF into rat brain increased BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was colocalized with the immature neuronal marker, doublecortin (Dcx). The increase in BrdUrd labeling after the administration of VEGF was caused by an increase in cell proliferation, rather than a decrease in cell death, because VEGF did not reduce caspase-3 cleavage in SVZ or SGZ. Cells labeled with BrdUrd after VEGF treatment in vivo include immature and mature neurons, astroglia, and endothelial cells. These findings implicate the angiogenesis factor VEGF in neurogenesis as well.