Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A.
Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A.
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整合素αvβ3介导的整合素α5β1和蛋白激酶A介导的内皮细胞迁移和血管生成的调节。
DOI：
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发表时间：
2000
影响因子：
4.8
通讯作者：
J. Varner
中科院分区：
文献类型：
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作者：
S. Kim;M. Harris;J. Varner
最近的研究表明，血管生成部分依赖于纤维连接蛋白对整合素α (5) β(1)的连接。现在有证据表明，整合素α (5) β(1)调节整合素α (v) β(3)对内皮细胞在体外迁移或体内血管生成过程中的功能。内皮细胞分泌纤维连接蛋白导致整合素α (5) β(1)的结扎，这增强了α (v) β(3)介导的向玻璃体连接蛋白的迁移，而不影响α (v) β(3)介导的细胞粘附。内皮细胞附着于玻璃体连接蛋白会抑制蛋白激酶A （PKA）的活性，而添加可溶性抗α (5) β(1)可以恢复这种活性。此外，激活细胞内PKA的药物，如福斯克林、二丁基cAMP或α (5) β(1)拮抗剂，在体外抑制内皮细胞在玻璃体连接蛋白上的迁移或在体内抑制血管生成。相反，PKA抑制剂逆转了α (5) β(1)拮抗剂介导的抗迁移或抗血管生成作用。因此，α (v) β(3)介导的内皮细胞迁移和血管生成可以通过PKA活性进行调控，这取决于整合素α (5) β(1)的连接状态。
Recent studies indicate that angiogenesis depends, in part, on ligation of integrin alpha(5)beta(1) by fibronectin. Evidence is now provided that integrin alpha(5)beta(1) regulates the function of integrin alpha(v)beta(3) on endothelial cells during their migration in vitro or angiogenesis in vivo. Secretion of fibronectin by endothelial cells leads to the ligation of integrin alpha(5)beta(1), which potentiates alpha(v)beta(3)-mediated migration on vitronectin without influencing alpha(v)beta(3)-mediated cell adhesion. Endothelial cell attachment to vitronectin suppresses protein kinase A (PKA) activity, while addition of soluble anti-alpha(5)beta(1) restores this activity. Moreover, agents that activate intracellular PKA, such as forskolin, dibutyryl cAMP or alpha(5)beta(1) antagonists, suppress endothelial cell migration on vitronectin in vitro or angiogenesis in vivo. In contrast, inhibitors of PKA reverse the anti-migratory or anti-angiogenic effects mediated by alpha(5)beta(1) antagonists. Therefore, alpha(v)beta(3)-mediated endothelial cell migration and angiogenesis can be regulated by PKA activity, which depends on the ligation state of integrin alpha(5)beta(1).