OSTEOPONTIN EXPRESSION IN CARDIOVASCULAR-DISEASES
OSTEOPONTIN EXPRESSION IN CARDIOVASCULAR-DISEASES
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DOI：
10.1111/j.1749-6632.1995.tb44624.x
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发表时间：
1995-01-01
期刊：
影响因子：
--
通讯作者：
ALMEIDA, M
中科院分区：
文献类型：
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作者：
GIACHELLI, CM;LIAW, L;ALMEIDA, M
黏附相互作用是公认的细胞在正常形态发生和疾病过程中的增殖、迁移和分化所必需的。通过差异克隆，骨桥蛋白被鉴定为一种黏附蛋白，在大鼠模型和包括动脉粥样硬化和再狭窄在内的人类血管疾病中，骨桥蛋白在血管重塑和新生内膜形成过程中上调。在功能研究中，纯化的骨桥蛋白促进血管平滑肌和内皮细胞的黏附、局灶性接触形成和迁移。利用中和抗体，发现三种整合素型受体，αvβ3，αvβ1和αvβ5支持细胞与骨桥蛋白的黏附。相比之下，只有含有αvβ3整合素的细胞才能向骨桥蛋白梯度迁移，这首次证明了骨桥蛋白的不同功能是通过不同的受体介导的。这些结果表明，骨桥蛋白通过其整合素型受体，通过促进血管平滑肌迁移和同时促进受影响区域的内皮覆盖，在发育和疾病过程中促进血管重构。
Adhesive interactions are recognized requirements for cellular proliferation, migration and differentiation during normal morphogenesis as well as disease. By differential cloning, osteopontin was identified as an adhesive protein upregulated during vascular remodeling and neointima formation in both rat models and human vascular diseases including atherosclerosis and restenosis. In functional studies, purified osteopontin promoted adhesion, focal contact formation, and migration of vascular smooth muscle and endothelial cells. Utilizing neutralizing antibodies, three integrin-type receptors, alpha v beta 3, alpha v beta 1, and alpha v beta 5 were found to support cellular adhesion to osteopontin. In contrast, only cells containing the alpha v beta 3 integrin could migrate towards an osteopontin gradient, demonstrating for the first time that different functions of osteopontin are mediated via distinct receptors. These results suggest a model whereby osteopontin, via its integrin-type receptors, contributes to vascular remodeling during development and disease by facilitating smooth muscle migration and simultaneously promoting endothelial coverage of the affected area.