The Role of Thrombomodulin in Diseases / 中国生物化学与分子生物学报

ABSTRACT

Thrombomodulin (TM) is a single-chain transmembrane glycoprotein that mainly exists in vascular endothelial cells, hematopoietic progenitor cells, monocytes and macrophages. TM is mainly composed of five structural regions the N-terminal lectin-like domain which plays a role in anti-inflammatory, and the six epidermal growth factor-like repeats which function as coagulation and fibrinolysis as well as serine-rich threonine regions and transmembrane domains and cytoplasmic domains. TM exhibits anti-inflammatory and anticoagulant effects by binding to thrombin to activate protein C, and TM-thrombin complex can also activate fibrinolytic inhibitors to suppress fibrinolysis. Previous reports showed that inhibiting epithelial mesenchymal transformation, mitogen-activated protein kinase or activating protein C and fibrinolytic inhibitor are the major mechanisms by which TM exerts anti-tumor properties. In atherosclerosis, TM can prevent atherosclerosis by blocking the activation of thrombin-mediated PAR-1 and inhibiting autophagy and apoptosis of endothelial cells. TM lectin-like domains can also bind to thrombin to inhibit its activity and further inhibit pulmonary thrombosis, fibrosis and inflammation. Moreover, TM protein is also involved in the pathogenesis of diabetic nephropathy, preeclampsia and ischemia-reperfu-sion injury. At present, TM is only clinically used for the treatment of sepsis and disseminated intravascular coagulation. Its role and therapeutic potential in cardiovascular and cerebrovascular diseases, cancers and other diseases deserve further exploration.