The vascular endothelial growth factor VEGF165 induces perlecan synthesis via VEGF receptor-2 in cultured human brain microvascular endothelial cells
The vascular endothelial growth factor VEGF165 induces perlecan synthesis via VEGF receptor-2 in cultured human brain microvascular endothelial cells
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DOI：
10.1016/j.bbagen.2006.06.010
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Wight, Thomas N.
中科院分区：
文献类型：
--
作者：
Kaji, Toshiyuki;Yamamoto, Chika;Wight, Thomas N.
作为血管内皮生长因子（VEGF）家族的一员，VEGF 165在微血管中以自分泌和旁分泌的方式调节血管内皮细胞的功能。蛋白聚糖是高度糖基化的多阴离子大分子，通过与细胞因子/生长因子相互作用影响细胞行为，如增殖和迁移。在本研究中，我们研究了VEGF 165对培养的人脑微血管内皮细胞中蛋白多糖合成的调节作用。将细胞暴露于重组人VEGF 165中，然后使用生化技术对蛋白聚糖进行表征。VEGF165处理使蛋白多糖在细胞层和条件培养基中的积累量分别增加1.4倍和1.6倍。这种效应是由VEGFR-2的激活引起的，并被维生素模仿，维生素是一种来自蛇毒的VEGFR-2配体，而不是胎盘生长因子，它特异性地与VEGFR-1结合。VEGF165刺激了perlecan的产生和分泌，取而代之的是较短的硫酸肝素侧链，但没有改变硫酸化双糖的组成。VEGF - 165刺激的内皮细胞分泌的perlecan可能参与血管生成、脑微血管疾病和内皮细胞单层的维持过程中细胞行为的调节。(c) 2006 Elsevier B.V.版权所有
A member of the vascular endothelial growth factor (VEGF) family, VEGF 165, regulates vascular endothelial cell functions in autocrine and paracrine fashions in microvessels. Proteoglycans are highly glycosylated poly-anionic macromolecules that influence cellular behaviors such as proliferation and migration by interacting with cytokines/growth factors. In the present study, we investigated the regulation of proteoglycan synthesis by VEGF 165 in cultured human brain microvascular endothelial cells. The cells were exposed to recombinant human VEGF 165, and the proteoglycans were then characterized using biochemical techniques. VEGF165 treatment increased the accumulation of proteoglycans 1.4- and 1.6-fold in the cell layer and conditioned medium, respectively. This effect resulted from the activation of VEGFR-2, and was mimicked by vammin, a VEGFR-2 ligand from snake venom but not placenta growth factor, which binds specifically to VEGFR-1. VEGF165 stimulated the production and secretion of perlecan, substituted with shorter heparan sulfate side chains, but with unaltered sulfated disaccharide composition. The perlecan secreted by VEGF 165-stimulated endothelial cells may be involved in the regulation of cellular behavior during angiogenesis, in diseases of the brain microvessels, and in the maintenance of the endothelial cell monolayer. (c) 2006 Elsevier B.V. All rights reserved.