Cadherin 6 has a functional role in platelet aggregation and thrombus formation.
Cadherin 6 has a functional role in platelet aggregation and thrombus formation.
复制标题
DOI：
10.1161/atvbaha.112.250464
复制
发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Kenny D
中科院分区：
文献类型：
--
作者：
Dunne E;Spring CM;Reheman A;Jin W;Berndt MC;Newman DK;Newman PJ;Ni H;Kenny D
血栓形成发生在血管损伤部位，当血小板与内皮下基质蛋白黏附并相互黏附时。血小板表达多种表面受体蛋白，但其中几种受体的功能尚不清楚。钙粘蛋白6在血小板表面表达，并含有精氨酸-甘氨酸-天冬氨酸基序，提示它可能在血栓形成中起支持作用。本研究的目的是研究钙粘蛋白6在血小板功能中的作用。抗体和外源性可溶性钙粘蛋白6均可抑制血小板聚集，精氨酸-甘氨酸-天冬氨酸-丝氨酸四肽抑制血小板与固定化钙粘蛋白6的黏附。抗αIIbβ3的抗体抑制了血小板与钙粘蛋白6的黏附。由于在纤维蛋白原和von Willebrand因子双缺陷小鼠中发生了血小板聚集，我们研究了钙粘蛋白6是否是整合素αIIbβ3的替代配体。本研究证明了钙粘蛋白6作为αIIbβ3的新配体的作用，并强调了其在血栓形成中的作用。
Thrombosis occurs at sites of vascular injury when platelets adhere to subendothelial matrix proteins and to each other. Platelets express many surface receptor proteins, the function of several of these remains poorly characterized. Cadherin 6 is expressed on the platelet surface and contains an arginine-glycine-aspartic acid motif, suggesting that it might have a supportive role in thrombus formation. The aim of this study was to characterize the role of cadherin 6 in platelet function. Platelet aggregation was inhibited by both antibodies and exogenous soluble cadherin 6. Platelet adhesion to immobilized cadherin 6 was inhibited by arginine-glycine-aspartic acid-serine tetrapeptides. Antibodies to αIIbβ3 inhibited platelet adhesion to cadherin 6. Because platelet aggregation occurs in fibrinogen and von Willebrand factor double-deficient mice, we investigated whether cadherin 6 is an alternative ligand for the integrin αIIbβ3. Platelet aggregation in fibrinogen and von Willebrand factor double-deficient mice was significantly inhibited by an antibody to cadherin 6. In flow-based assays, inhibition of cadherin 6 caused a marked reduction in thrombus formation in both human and mouse blood. This study demonstrates the role of cadherin 6 as a novel ligand for αIIbβ3 and highlights its function in thrombus formation.