CD36: A critical anti-angiogenic receptor
CD36: A critical anti-angiogenic receptor
复制标题
DOI：
10.2741/1168
复制
发表时间：
2003-09-01
影响因子：
3.1
通讯作者：
Silverstein, RL
中科院分区：
文献类型：
--
作者：
Simantov, R;Silverstein, RL
Thrombospondin-1 (TSP-1) 是体内血管生成和体外微血管内皮细胞对血管生成因子反应的有效抑制剂。 CD36 是微血管内皮上 TSP-1 的细胞受体，是其抗血管生成活性所必需的。 TSP-1 的抗血管生成活性包含在称为 TSP I 型重复序列 (TSR-1) 的结构域中。 TSR-1 结构域存在于许多其他蛋白质中，其中一些也被证明具有抗血管生成活性。结构功能分析已确定 TSP-1 与 CD36 的结合是通过 TSP 的 TSR-1 结构域与 CD36 中称为 CLESH-1 的保守结构域相互作用介导的。富含组氨酸的糖蛋白是一种血浆和细胞蛋白，可阻断血小板反应蛋白-1 与 CD36 的结合，抑制对血小板反应蛋白的抗血管生成反应，并可能用于调节血小板反应蛋白/CD36 抗血管生成途径。一些体内模型支持 TSP/CD36 系统在血管生成和肿瘤生长中的作用，并提供证据表明 CD36 抗血管生成途径提供了有吸引力的治疗靶点。
Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis in vivo and of microvascular endothelial cell responses to angiogenic factors in vitro. CD36 is the cellular receptor for TSP-1 on microvascular endothelium and is necessary for its anti-angiogenic activity. The anti-angiogenic activity of TSP-1 is contained in a structural domain known as the TSP type I repeat (TSR-1). TSR-1 domains occur in many other proteins, some of which have also been shown to have anti-angiogenic activity. Structure-function analyses have determined that binding of TSP-1 to CD36 is mediated by interaction of the TSR-1 domain of TSP with a conserved domain called CLESH-1 in CD36. Histidine rich glycoprotein, a plasma and cellular protein that blocks the binding of thrombospndin-1 to CD36, inhibits the antiangiogenic response to thrombospondin and may serve to modulate the thrombospondin/CD36 anti-angiogenic pathway. Several in vivo models support the role of the TSP/CD36 system in angiogenesis and tumor growth and provide evidence that the CD36 antiangiogenic pathway offers attractive therapeutic targets.