Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, United Kingdom.
J Clin Invest. 2019 Jan 2;129(1):12-23. doi: 10.1172/JCI122955.
Although platelets are best known for their role in hemostasis, they are also crucial in development, host defense, inflammation, and tissue repair. Many of these roles are regulated by the immune-like receptors glycoprotein VI (GPVI) and C-type lectin receptor 2 (CLEC-2), which signal through an immunoreceptor tyrosine-based activation motif (ITAM). GPVI is activated by collagen in the subendothelial matrix, by fibrin and fibrinogen in the thrombus, and by a remarkable number of other ligands. CLEC-2 is activated by the transmembrane protein podoplanin, which is found outside of the vasculature and is upregulated in development, inflammation, and cancer, but there is also evidence for additional ligands. In this Review, we discuss the physiological and pathological roles of CLEC-2 and GPVI and their potential as targets in thrombosis and thrombo-inflammatory disorders (i.e., disorders in which inflammation plays a critical role in the ensuing thrombosis) relative to current antiplatelet drugs.
虽然血小板以其在止血中的作用而闻名，但它们在发育、宿主防御、炎症和组织修复中也起着关键作用。这些作用中的许多是由免疫样受体糖蛋白 VI（GPVI）和 C 型凝集素受体 2（CLEC-2）调节的，它们通过免疫受体酪氨酸激活基序（ITAM）发出信号。GPVI 被位于亚内皮基质中的胶原、血栓中的纤维蛋白和纤维蛋白原以及许多其他配体激活。CLEC-2 被跨膜蛋白 podoplanin 激活，该蛋白存在于脉管系统之外，在发育、炎症和癌症中上调，但也有其他配体的证据。在这篇综述中，我们讨论了 CLEC-2 和 GPVI 的生理和病理作用及其作为血栓形成和血栓炎症性疾病（即炎症在随后的血栓形成中起关键作用的疾病）靶点的潜力，相对于当前的抗血小板药物。
