Physiological and pathophysiological aspects of blood platelet activation through CLEC-2 receptor

Abstract

Platelet activating receptor CLEC-2 has been identified on platelet surface a decade ago. The only confirmed endogenous CLEC-2 agonist is podoplanin. Podoplanin is a transmembrane protein expressed by lymphatic endothelial cells, reticular fibroblastic cells in lymph nodes, kidney podocytes and by cells of certain tumors. Association of CLEC-2 with podoplanin is involved in processes of embryonic development (blood-lymph vessel separation and angiogenesis), maintaining of vascular integrity of small vessels during inflammation and prevention of blood-lymphatic mixing in high endothelial venules. However, CLEC-2 and podoplanin are contributing to tumor metastasis progression, Salmonella sepsis and deep-vein thrombosis. This makes CLEC-2 and podoplanin a perspective target for pharmacological treatment. Aspirin and Ibrutinib are considered to be perspective for abrogation of podoplanin-induced platelet activation via CLEC-2. The present review discusses already known pathological and physiological roles of CLEC-2 and possibilities of a targeted therapy for CLEC-2 associated diseases.

Keywords

• platelet
• molecular signaling
• tyrosine-kinases
• clec-2
• metastasis
• deep vein thrombosis