thrombomoduliini

Thrombomoduliini, commonly referred to as thrombomodulin, is a transmembrane glycoprotein expressed primarily on vascular endothelial cells. Its main function is to serve as a cofactor for thrombin, redirecting thrombin’s proteolytic activity toward activation of protein C. Activated protein C (APC), with its cofactor protein S, rapidly inactivates coagulation factors Va and VIIIa, thereby reducing thrombin generation and exerting an anticoagulant effect. In addition, APC signaling through the endothelial protein C receptor (EPCR) contributes to cytoprotective and anti-inflammatory responses.

The molecule has a distinct extracellular structure that includes an N-terminal C-type lectin-like domain, six epidermal growth factor (EGF)-like repeats, and a serine/threonine-rich domain, followed by a single transmembrane segment and a short cytoplasmic tail. The extracellular region is responsible for thrombin binding, while proteolytic shedding can release a soluble form of thrombomodulin into the circulation, reflecting endothelial injury.

Expression and regulation: Thrombomodulin is predominantly expressed on the luminal surface of endothelial cells in many tissues. Its expression and shedding are modulated by inflammatory cytokines, oxidative stress, and other pathological stimuli. Elevated levels of soluble thrombomodulin in plasma are associated with endothelial damage and conditions such as sepsis, burns, and disseminated intravascular coagulation (DIC).

Clinical relevance: Thrombomodulin plays a central role in maintaining hemostatic balance and protecting the endothelium from excessive coagulation. Soluble thrombomodulin is used as a biomarker of endothelial injury in research and clinical settings. Recombinant human soluble thrombomodulin (rhTM) has been used as a therapeutic agent for DIC in certain countries, with regulatory status varying by region.