Deletion of platelet STK10 impairs deep vein thrombus formation.

Abstract

BACKGROUND: Serine-threonine kinase 10 (STK10) is a member of Ste20 family of serine/threonine kinases. Our previous study showed STK10 is expressed in platelets and regulates platelet function in arterial thrombosis. Whether it plays a role in venous thrombosis remains unclear. OBJECTIVES: In this study, we aim to investigate the role of platelet STK10 in deep vein thrombosis (DVT) by using platelet-specific STK10 knockout mice. METHODS: A DVT model was constructed via ligation of the inferior vena cava, and 24 hours later, an inferior vena cava sample was obtained for analysis of thrombi length and weight, the accumulation of platelets, neutrophils, platelet-neutrophil interaction, neutrophil extracellular traps (NET) formation, and platelet procoagulant function by immunofluorescence staining. RESULTS: During the development of DVT in mouse models, a significantly increased STK10 phosphorylation along with an increase of integrin-linked protein kinase phosphorylation (Ser343) was observed in the platelets. Deletion of platelet STK10 reduced the incidence and severity of DVT and inhibited platelet activation, platelet-neutrophil interaction, the recruitment and accumulation of platelets and neutrophils, and NET formation in the venous thrombin. In addition, absence of platelet STK10 inhibits NET formation induced by thrombin-stimulated platelets in vitro. Moreover, deficiency of platelet STK10 decreased platelet procoagulant activity in the peripheral blood and venous thrombi. CONCLUSION: Our study shows a novel regulatory role of platelet STK10 in the development and pathogenesis of DVT, implying that targeting platelet STK10 might be a novel approach for the prevention and treatment of venous thrombosis.