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.

Analysis of platelet RNA: a non-invasive method for studying the expression of tumor genes

“…Подопланин способен напрямую связываться с лектин-подобным рецептором С-типа 2 (CLEC-2), который экспрессируется на поверхности миелоидных клеток, NK-клеток, а также тромбоцитов [58]. Связывание CLEC-2 с подопланином приводит к активации тромбоцитов, включающей секрецию АДФ и синтез TXA 2 [59,60]. Takagi и соавт.…”

Platelet functional responses and signalling: the molecular relationship. Part 1: responses.

“…Blood platelets play a critical role in this response. They actually have a number of critical roles in human physiology, which include formation of the hemostatic plug upon injury [2], acceleration of the membrane-dependent reactions of blood coagulation [3,4], maintenance of vascular integrity [5][6][7], modulation of immune responses [8][9][10], tissue growth and regeneration [11,12]. In order to perform these urgent functions when and where it is needed, platelets rely on their huge network of receptors and signal transduction pathways.…”

Platelet functional responses and signalling: the molecular relationship. Part 2: receptors.

“…Platelets are blood cells that play a key role in the process of stopping bleeding [1] ], as well as in the formation of a hemostatic plug in trauma [2], maintaining the integrity of blood vessels [3][4][5] and modulating immune responses [6][7][8]. The protein composition of platelets is predetermined, although minor de novo protein synthesis is still present [9].…”