Integrin α9β1 directly binds to vascular endothelial growth factor (VEGF)- a and contributes to VEGF-A-induced angiogenesis
Integrin α9β1 directly binds to vascular endothelial growth factor (VEGF)- a and contributes to VEGF-A-induced angiogenesis
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DOI：
10.1074/jbc.m609323200
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发表时间：
2007-05-18
影响因子：
4.8
通讯作者：
Sheppard, Dean
中科院分区：
文献类型：
--
作者：
Vlahakis, Nicholas E.;Young, Bradford A.;Sheppard, Dean
血管内皮生长因子A（VEGF-A）是一种强有力的血管生成诱导剂。我们现在发现VEGF-A诱导的人内皮细胞粘附和迁移依赖于整合素α 9 β 1，并且VEGF-A是该整合素的直接配体。这些细胞在VEGF-A的165和121同种型上的粘附和迁移依赖于来自α 9 β 1和VEGF-A的同源受体VEGF受体2（VEGF-R2）的协同输入。与α 3 β 1或α v β 3整联蛋白不同，还发现α 9 β 1结合VEGF-A的121同种型。这种相互作用似乎具有生物学意义，因为α 9 β 1阻断抗体显著且特异性地抑制VEGF-A165或-121诱导的血管生成。结合我们先前的发现，α 9 β 1直接结合VEGF-C和-D，并有助于淋巴管生成，这些结果确定整合素α 9 β 1作为潜在的药理学靶点，用于抑制致病性血管生成和淋巴管生成。
Vascular endothelial growth factor A (VEGF-A) is a potent inducer of angiogenesis. We now show that VEGF-A-induced adhesion and migration of human endothelial cells are dependent on the integrin alpha 9 beta 1 and that VEGF-A is a direct ligand for this integrin. Adhesion and migration of these cells on the 165 and 121 isoforms of VEGF-A depend on cooperative input from alpha 9 beta 1 and the cognate receptor for VEGF-A, VEGF receptor 2 (VEGF-R2). Unlike alpha 3 beta 1 or alpha v beta 3 integrins, alpha 9 beta 1 was also found to bind the 121 isoform of VEGF-A. This interaction appears to be biologically significant, because alpha 9 beta 1-blocking antibody dramatically and specifically inhibited angiogenesis induced by VEGF-A165 or -121. Together with our previous findings that alpha 9 beta 1 directly binds to VEGF-C and -D and contributes to lymphangiogenesis, these results identify the integrin alpha 9 beta 1 as a potential pharmacotherapeutic target for inhibition of pathogenic angiogenesis and lymphangiogenesis.