Quantification and cell-to-cell variation of vascular endothelial growth factor receptors.

Quantification and cell-to-cell variation of vascular endothelial growth factor receptors.
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DOI:
10.1016/j.yexcr.2010.12.014
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发表时间:
2011-04-15
影响因子:
3.7
通讯作者:
Popel AS
Popel AS
中科院分区:
医学3区
文献类型:
--
作者:
Imoukhuede PI;Popel AS

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血管内皮生长因子受体(VEGFR)在血管生成中起重要作用,即从现有血管系统形成新血管。系统生物学提供了有前途的方法,以更好地了解血管生成的计算模型,在这个过程中的关键分子相互作用。这种建模需要定量了解促血管生成受体与抗血管生成受体的细胞表面密度、它们的调节以及它们的细胞间变异性。使用定量荧光,我们系统地表征了血管内皮生长因子受体和神经纤毛蛋白-1(NRP 1)的内皮表面密度。我们还确定了VEGF在调节这些受体的表面密度中的作用。应用逐细胞分析揭示了受体表面密度的异质性和VEGF对这种异质性的调节。总之,我们确定这些受体的表面表达水平的固有差异和VEGF在调节抗血管生成或调节(VEGFR 1)和促血管生成(VEGFR 2)受体的平衡中的作用。
The vascular endothelial growth factor receptors (VEGFR) play a significant role in angiogenesis, the formation of new blood vessels from existing vasculature. Systems biology offers promising approaches to better understand angiogenesis by computational modeling the key molecular interactions in this process. Such modeling requires quantitative knowledge of cell surface density of pro-angiogenic receptors versus anti-angiogenic receptors, their regulation, and their cell-to-cell variability. Using quantitative fluorescence, we systematically characterized the endothelial surface density of VEGFRs and neuropilin-1 (NRP1). We also determined the role of VEGF in regulating the surface density of these receptors. Applying cell-by-cell analysis revealed heterogeneity in receptor surface density and VEGF tuning of this heterogeneity. Altogether, we determine inherent differences in the surface expression levels of these receptors and the role of VEGF in regulating the balance of anti-angiogenic or modulatory (VEGFR1) and pro-angiogenic (VEGFR2) receptors.
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