Focal adhesion kinase is required for blood vessel morphogenesis
Focal adhesion kinase is required for blood vessel morphogenesis
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DOI：
10.1161/01.res.0000055016.36679.23
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发表时间：
2003-02-21
影响因子：
20.1
通讯作者：
Damsky, CH
中科院分区：
文献类型：
--
作者：
Ilic, D;Kovacic, B;Damsky, CH
非受体酪氨酸激酶粘着斑激酶（FAK）是细胞外基质、可溶性因子和机械刺激信号的汇聚点。在小鼠中靶向破坏fak基因导致胚胎第8.5天（E8.5）死亡。FAK（-/-）胚胎的血管发育严重受损。基因表达和体外分化研究表明，内皮细胞分化在FAK（-/-）和野生型E8.5胚胎相当。我们使用体外小管形成试验和三种不同的培养系统检测了FAK在血管形态发生中的作用：FAK（+/+）和FAK（-/-）胚状体，FAK（+/+）和FAK（-/-）内皮细胞，以及表达反义FAK、FAK的显性阴性片段或野生型FAK的人脐静脉内皮细胞。在所有这些系统中，FAK表达或功能缺陷的内皮细胞在基质胶中形成小管的能力严重降低。这些研究清楚地表明，FAK（-/-）小鼠的血管缺陷是由于FAK缺陷的内皮细胞不能将自己组织成血管网络，而不是由于组织特异性分化的缺陷。
The nonreceptor tyrosine kinase focal adhesion kinase (FAK) is a point of convergence for signals from extracellular matrix, soluble factors, and mechanical stimuli. Targeted disruption of the fak gene in mice leads to death at embryonic day 8.5 (E8.5). FAK(-/-) embryos have severely impaired blood vessel development. Gene expression and in vitro differentiation studies revealed that endothelial cell differentiation was comparable in FAK(-/-) and wild-type E8.5 embryos. We examined the role of FAK in blood vessel morphogenesis using an in vitro tubulogenesis assay and three different culture systems: FAK(+/+) and FAK(-/-) embryoid bodies, FAK(+/+) and FAK(-/-) endothelial cells, and human umbilical vein endothelial cells expressing antisense FAK, a dominant- negative fragment of FAK, or wild-type FAK. In all of these systems, endothelial cells deficient in FAK expression or function displayed a severely reduced ability to form tubules in Matrigel. These studies demonstrate clearly that the vascular defects in FAK(-/-) mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular networks, rather than from defects in tissue-specific differentiation.