Role of GPR56 in Platelet Activation and Arterial Thrombosis
Role of GPR56 in Platelet Activation and Arterial Thrombosis
复制标题
DOI：
10.1055/a-1983-0457
复制
发表时间：
2022-01
影响因子：
6.7
通讯作者：
Dongsheng Liu;Peng Zhang;Kandi Zhang;Changlong Bi;Li Li-Li;Yanyan Xu;Tiantian Zhang;Junfeng Zhang
中科院分区：
文献类型：
--
作者：
Dongsheng Liu;Peng Zhang;Kandi Zhang;Changlong Bi;Li Li-Li;Yanyan Xu;Tiantian Zhang;Junfeng Zhang
粘附G蛋白偶联受体GPR56介导细胞-细胞和细胞-细胞外基质相互作用。为了研究GPR56在血小板活化和动脉血栓形成中的功能，我们制造了GPR56敲除小鼠，并评估了GPR56在人和小鼠血小板中的表达。结果显示，st段抬高型心肌梗死患者血浆GPR56 n端片段水平在心肌梗死后第1天明显高于第7天。接下来，我们在体外和体内研究了GPR56对血小板功能的影响。我们观察到胶原诱导的聚集和三磷酸腺苷释放在Gpr56−/−血小板中减少。此外，Gpr56−/−血小板表面p -选择素的表达也减少，固定化胶原在Gpr56−/−血小板上的扩散面积减少。此外，抗gpr56抗体可抑制胶原诱导的人血小板活化。Gpr56−/−小鼠在颈动脉激光损伤模型和fecl3诱导的颈动脉损伤模型中显示出较长的首次闭塞时间。GPR56激活胶原刺激后的G蛋白13信号通路，促进血管损伤部位血小板粘附和血栓形成。因此，我们的研究证实GPR56调节动脉血栓形成。抑制GPR56对胶原蛋白的初始反应可显著抑制血小板活化和血栓形成。我们的研究结果为抗血小板药物的研究提供了新的见解。
Abstract The adhesion G protein-coupled receptor GPR56 mediates cell–cell and cell–extracellular matrix interactions. To examine the function of GPR56 in platelet activation and arterial thrombosis, we generated GPR56-knockout mice and evaluated GPR56 expression in human and mouse platelets. The results revealed that the levels of the GPR56 N-terminal fragment were significantly higher on the first day after myocardial infarction than on the seventh day in the plasma of patients with ST-segment-elevation myocardial infarction. Next, we investigated the effects of GPR56 on platelet function in vitro and in vivo. We observed that collagen-induced aggregation and adenosine triphosphate release were reduced in Gpr56 −/− platelets. Furthermore, P-selectin expression on the Gpr56 −/− platelet surface was also reduced, and the spreading area on immobilized collagen was decreased in Gpr56 −/− platelets. Furthermore, collagen-induced platelet activation in human platelets was inhibited by an anti-GPR56 antibody. Gpr56 −/− mice showed an extended time to the first occlusion in models with cremaster arteriole laser injury and FeCl 3 -induced carotid artery injury. GPR56 activated the G protein 13 signaling pathway following collagen stimulation, which promoted platelet adhesion and thrombus formation at the site of vascular injury. Thus, our study confirmed that GPR56 regulated the formation of arterial thrombosis. Inhibition of the initial response of GPR56 to collagen could significantly inhibit platelet activation and thrombus formation. Our results provide new insights for research into antiplatelet drugs.