The Multifaceted Roles of Thrombomodulin: Anti-coagulation, Anti-inflammation, and Anti-tumor Potential

Thrombomodulin (TM) is a single-chain transmembrane glycoprotein with anticoagulant effects. TM has two forms: membrane type existing on the cell surface and blood type free in plasma and urine. TM functions as an anticoagulant cofactor for thrombin activation of protein C on the surface of vascular endothelial cells. Due to the excellent anti-coagulant effects in modulating the coagulation and fibrinolytic system, the recombinant human soluble TM (rhsTM) has been used for the treatment of disseminated intravascular coagulation (DIC). In addition to anti-coagulation, many studies have shown that TM can also exert anti-inflammatory and anti-tumor effects. TM has a lectin-like domain at its N-terminus that has been shown to exhibit direct anti-inflammatory functions. At the same time, due to its special structure, thrombomodulin plays an important role in vascular-related mechanistic diseases by participating in the regulation of inflammatory pathways, complement, HMGB1, etc. In this article, changes in TM expression in the body after injury, composition of TM structural domains, anticoagulant, anti-inflammatory, and antitumor effects, and related mechanisms of TM were systematically reviewed, to provide a theoretical basis and reference for the potential clinical implications of TM in treating various diseases.