A role of the novel platelet activation receptor CLEC-2 and its internal ligand podoplanin in thrombotic diseases

新型血小板活化受体CLEC-2与多种癌细胞表面表达的podoplanin结合，促进肿瘤转移。然而，其在血栓和止血中的作用至今尚未阐明。我们制造了clc -2缺陷小鼠，发现血栓形成在体内和体外都受到抑制。我们还发现，CLEC-2以依赖于血小板活化的方式形成亲同性结合，从而稳定血栓形成。缺乏CLEC-2的血小板尾出血未明显增加，提示CLEC-2可能是抗血小板药物的良好靶蛋白，其抑制病理性血栓形成，但不抑制生理性止血。

Novel platelet activation receptor CLEC-2 binds to podoplanin expressed on the surface of several kinds of cancer cells, which facilitates cancer metastasis. However, its role in thrombosis and hemostasis has not been elucidated to date. We generated CLEC-2-deficient mice and found that thrombus formation was inhibited in vivo and in vitro. We also found that CLEC-2 forms homophilic association in a manner depending on platelet activation, which stabilizes thrombus formation. Tail bleeding was not significantly increased in CLEC-2-deficient platelets, suggesting that CLEC-2 may be a good target protein for anti-platelet drug, which inhibits pathological thrombosis, but not physiological hemostasis.