BASIC FIBROBLAST GROWTH-FACTOR MODULATES INTEGRIN EXPRESSION IN MICROVASCULAR ENDOTHELIAL-CELLS
BASIC FIBROBLAST GROWTH-FACTOR MODULATES INTEGRIN EXPRESSION IN MICROVASCULAR ENDOTHELIAL-CELLS
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DOI：
10.1091/mbc.4.10.973
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发表时间：
1993-10-01
影响因子：
3.3
通讯作者：
RIFKIN, DB
中科院分区：
文献类型：
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作者：
KLEIN, S;GIANCOTTI, FG;RIFKIN, DB
在血管生成过程中，毛细血管内皮细胞在与细胞外基质成分的相互作用中经历了一系列协调的修饰。在这项研究中，我们研究了原型血管生成因子碱性成纤维细胞生长因子（bFGF）的微血管内皮细胞的几个整合素的表达和功能的影响。免疫沉淀实验表明，微血管细胞表达在其表面的几个整合素的抗体的各个亚基。这些包括α 1 β 1、α 2 β 1和α 3 β 1层粘连蛋白/胶原蛋白受体; α 6 β 1层粘连蛋白受体; α 5 β 1和α v β 1纤连蛋白受体; α 6 β 4基底膜受体;以及α v β 3和α v β 5玻连蛋白受体。用bFGF治疗引起α 2 β 1、α 3 β 1、α 5 β 1、α 6 β 1、α 6 β 4和α v β 5整合素的表面表达显著增加。相反，α 1 β 1和α v β 3整合素的表达水平在bFGF处理的细胞中降低。代谢标记细胞的免疫沉淀表明，bFGF增加α 3，α 5，α 6，β 4和β 5亚基的生物合成，并减少α v和β 3亚基的产生。这些结果表明bFGF通过改变单个α或β亚基的生物合成来调节整合素的表达。根据在bFGF处理的细胞中观察到的几种整合素的上调，这些细胞比未处理的细胞更好地粘附于纤连蛋白、层粘连蛋白、玻连蛋白和I型胶原。β 1整合素表达的最大差异发生在暴露于bFGF后72小时，此时内皮细胞与细胞粘附分子endoCAM的表达也显著上调。与此相反，在相同的细胞中，最大诱导纤溶酶原激活物的产生需要较短的暴露于bFGF（24-48小时）。两者合计，这些结果表明，bFGF引起微血管内皮细胞中几种整合素的表达和功能水平的显着变化。
During angiogenesis capillary endothelial cells undergo a coordinated set of modifications in their interactions with extracellular matrix components. In this study we have investigated the effect of the prototypical angiogenic factor basic fibroblast growth factor (bFGF) on the expression and function of several integrins in microvascular endothelial cells. Immunoprecipitation experiments with antibodies to individual subunits indicated that microvascular cells express at their surface several integrins. These include the alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 laminin/collagen receptors; the alpha 6 beta 1 laminin receptor; the alpha 5 beta 1 and alpha v beta 1 fibronectin receptors; the alpha 6 beta 4 basement membrane receptor; and the alpha v beta 3 and alpha v beta 5 vitronectin receptors. Treatment with bFGF caused a significant increase in the surface expression of the alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 5 integrins. In contrast, the level of expression of the alpha 1 beta 1 and alpha v beta 3 integrins was decreased in bFGF-treated cells. Immunoprecipitation of metabolically labeled cells indicated that bFGF increases the biosynthesis of the alpha 3, alpha 5, alpha 6, beta 4, and beta 5 subunits and decreases the production of the alpha v and beta 3 subunits. These results suggest that bFGF modulates integrin expression by altering the biosynthesis of individual alpha or beta subunits. In accordance with the upregulation of several integrins observed in bFGF-treated cells, these cells adhered better to fibronectin, laminin, vitronectin, and type I collagen than did untreated cells. The largest differences in beta 1 integrin expression occurred similar to 72 h after exposure to bFGF, at a time when the expression of the endothelial cell-to-cell adhesion molecule endoCAM was also significantly upregulated. In contrast, a shorter exposure to bFGF (24-48 h) was required for the maximal induction of plasminogen activator production in the same cells. Taken together, these results show that bFGF causes significant changes in the level of expression and function of several integrins in microvascular endothelial cells.