Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival
Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival
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DOI：
10.1016/j.ydbio.2003.08.015
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发表时间：
2003-12-01
影响因子：
2.7
通讯作者：
D'Amore, PA
中科院分区：
文献类型：
--
作者：
Darland, DC;Massingham, LJ;D'Amore, PA
周细胞已被认为在调节血管稳定性中发挥作用;这种稳定的一种机制可能是通过周细胞衍生的血管内皮生长因子（VEGF）。为了验证间充质细胞分化为周细胞/平滑肌细胞（SMC）伴随VEGF表达的假设，我们使用内皮细胞（EC）和间充质细胞共培养来模拟血管发育过程中发生的细胞-细胞相互作用。EC和10 T1/2细胞（多能间充质细胞）共培养导致10 T1/2细胞诱导VEGF表达。VEGF表达的增加依赖于EC-10 T1/2之间的接触，并由转化生长因子β（TGF β）介导。在共培养中产生的大多数VEGF是细胞和/或基质相关的。用高盐、醇溶谷蛋白、肝素或苏拉明处理细胞释放显著的VEGF，表明硫酸乙酰肝素蛋白聚糖可能螯合了一些VEGF。共培养物中VEGF的抑制导致EC凋亡增加75%，表明共培养物中EC的存活依赖于10 T1/2衍生的VEGF。VEGF基因表达在视网膜血管发育中的周细胞接触新形成的nucrovessels观察。我们的观察结果表明，分化的周细胞产生VEGF，可能作为一个生存和/或稳定因素EC微血管中的一种促分泌/旁分泌的方式。(C)2003年爱思唯尔公司All rights reserved.
Pericytes have been suggested to play a role in regulation of vessel stability; one mechanism for this stabilization may be via pericyte-derived vascular endothelial growth factor (VEGF). To test the hypothesis that differentiation of mesenchymal cells to pericytes/smooth muscle cells (SMC) is accompanied by VEGF expression, we used endothelial cell (EC) and mesenchymal cell cocultures to model cell-cell interactions that occur during vessel development. Coculture of EC and 10T1/2 cells, multipotent mesenchymal cells, led to induction of VEGF expression by 10T1/2 cells. Increased VEGF expression was dependent on contact between EC-10T1/2 and was mediated by transforming growth factorbeta (TGFbeta). A majority of VEGF produced in coculture was cell- and/or matrix-associated. Treatment of cells with high salt, prolamine, heparin, or suramin released significant VEGF, suggesting that heparan sulfate proteoglycan might be sequestering some of the VEGF. Inhibition of VEGF in cocultures led to a 75% increase in EC apoptosis, indicating that EC survival in cocultures is dependent on 10T1/2-derived VEGF. VEGF gene expression in developing retinal vasculature was observed in pericytes contacting newly formed nucrovessels. Our observations indicate that differentiated pericytes produce VEGF that may act in a juxtacrine/paracrine manner as a survival and/or stabilizing factor for EC in microvessels. (C) 2003 Elsevier Inc. All rights reserved.