Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens
Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens
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DOI：
10.1016/j.bbrc.2008.07.123
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发表时间：
2008-10-03
影响因子：
3.1
通讯作者：
Hashizume, Kiyoshi
中科院分区：
文献类型：
--
作者：
Nakamura, Junko;Shigematsu, Satoshi;Hashizume, Kiyoshi
内皮细胞的迁移和管形成在血管生成中是重要的，并且需要对细胞外基质（ECM）和生长因子的协调反应。由于黏着斑激酶（FAK）整合了ECM和生长因子的信号，我们研究了其在血管生成中的作用。I型和II型胶原是形成原纤维的胶原，并刺激人脐静脉内皮细胞（HUVEC）形成管状结构。虽然敲低FAK抑制细胞运动，并导致抑制管形成，FAK降解和管形成后，同时发生与原纤维形成胶原孵育。钙蛋白酶抑制剂对FAK降解的补偿或FAK的瞬时过表达导致了小管形成的障碍。这些现象是纤维形成胶原蛋白所特有的，并通过α 2 β 1整联蛋白介导。总之，我们的数据表明，FAK在细胞迁移中起作用，但纤维形成胶原诱导的FAK降解是必要的内皮管形成。(c)2008年爱思唯尔公司All rights reserved.
Migration and tube formation of endothelial cells are important in angiogenesis and require a coordinated response to the extra-cellular matrix (ECM) and growth factor. Since focal adhesion kinase (FAK) integrates signals from both ECM and growth factor, we investigated its role in angiogenesis. Type I and II collagens are fibril-forming collagens and stimulate human umbilical vein endothelial cells (HUVECs) to form tube structure. Although knockdown of FAK restrained cell motility and resulted in inhibition of tube formation, FAK degradation and tube formation occurred simultaneously after incubation with fibril-forming collagens. The compensation for the FAK degradation by a calpain inhibitor or transient over-expression of FAK resulted in disturbance of tube formation. These phenomena are specific to fibril-forming collagens and mediated via alpha 2 beta 1 integrin. In conclusion, our data indicate that FAK is functioning in cell migration, but fibril-forming collagen-induced FAK degradation is necessary for endothelial tube formation. (c) 2008 Elsevier Inc. All rights reserved.