Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin αvβ3 on vascular endothelial cells
Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin αvβ3 on vascular endothelial cells
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DOI：
10.1002/jcp.1122
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发表时间：
2001-09-01
影响因子：
5.6
通讯作者：
Sato, Y
中科院分区：
文献类型：
--
作者：
Terai, Y;Abe, M;Sato, Y
血管平滑肌细胞生长促进因子（VSGP）最初是从牛卵巢卵泡液中分离出来的，作为血管平滑肌细胞增殖的刺激因子。同源性搜索表明，牛和人类VSGPs是大鼠F-脊椎蛋白的直系同源物。在这里，我们研究了重组人VSGP/F-spondin是否影响内皮细胞的生物活性。VSGP/F-spondin不影响人脐静脉内皮细胞（HUVEC）的增殖，但是，它确实抑制VEGF或bFGF刺激的HUVEC迁移。为了阐明这种抑制作用的机制，我们检查了HUVEC与细胞外基质蛋白的粘附。VSGP/F-spondin通过功能性阻断整合素α nu β 3特异性抑制HUVEC在玻连蛋白上的扩散。结果表明，VSGP/F-spondin抑制了粘附斑激酶（FAK）的酪氨酸磷酸化。此外，VSGP/F-spondin抑制Akt的激活时，在玻连蛋白上的HUVECs与VEGF刺激。VSGP/F-spondin在体外抑制HUVECs管形成，在体内抑制大鼠角膜新生血管形成。这些结果表明VSGP/F-spondin至少部分通过阻断内皮整合素α nu β 3来抑制血管生成。
Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here; we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin alpha nu beta3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin alpha nu beta3.