Lactadherin promotes VEGF-dependent neovascularization
Lactadherin promotes VEGF-dependent neovascularization
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DOI：
10.1038/nm1233
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发表时间：
2005-05-01
期刊：
影响因子：
82.9
通讯作者：
Mallat, Z
中科院分区：
文献类型：
--
作者：
Silvestre, JS;Théry, C;Mallat, Z
血管内皮生长因子（VEGF）诱导的血管生长参与生理和病理性血管生成，并需要整合素介导的信号转导。我们现在表明，整合素结合蛋白最初描述的乳脂球，MFG-E8（也称为lactadherin），表达在血管和周围，并在VEGF依赖的新生血管在成年小鼠中的关键作用。使用中和抗体和lactadherin缺陷的动物，我们发现lactadherin与α v β 3和α v β 5整合素相互作用，并改变VEGF依赖性Akt磷酸化和新血管形成。在VEGF不存在的情况下，乳黏附素给药在体外诱导内皮细胞中的α v β 3-和α v β 5-依赖性Akt磷酸化，并在体内强烈改善缺血后新血管形成。这些结果表明，乳粘附素在VEGF依赖性新生血管形成中起着至关重要的作用，并将乳粘附素确定为调节新生血管形成的重要靶点。
Vascular endothelial growth factor (VEGF)-induced blood vessel growth is involved in both physiological and pathological angiogenesis and requires integrin-mediated signaling. We now show that an integrin-binding protein initially described in milk-fat globule, MFG-E8 (also known as lactadherin), is expressed in and around blood vessels and has a crucial role in VEGF-dependent neovascularization in the adult mouse. Using neutralizing antibodies and lactadherin-deficient animals, we show that lactadherin interacts with alpha v beta 3 and alpha v beta 5 integrins and alters both VEGF-dependent Akt phosphorylation and neovascularization. In the absence of VEGF, lactadherin administration induced alpha v beta 3- and alpha v beta 5-dependent Akt phosphorylation in endothelial cells in vitro and strongly improved postischemic neovascularization in vivo. These results show a crucial role for lactadherin in VEGF-dependent neovascularization and identify lactadherin as an important target for the modulation of neovascularization.