Suzuki Koji
Professor, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.
Vice President for Research, Suzuka University of Medical Science, Suzuka, Mie, Japan.
Proc Jpn Acad Ser B Phys Biol Sci. 2025 Feb 10;101(2):75-97. doi: 10.2183/pjab.101.006. Epub 2024 Dec 18.
Thrombomodulin (TM) is an important regulator of intravascular blood coagulation, fibrinolysis, and inflammation. TM inhibits the procoagulant and proinflammatory activities of thrombin and promotes the thrombin-induced activation of protein C (PC) bound to the endothelial PC receptor (EPCR). Activated PC (APC) inactivates coagulation factors Va and VIIIa, thereby inhibiting blood clotting. APC bound to EPCR exerts anti-inflammatory and cytoprotective effects on vascular endothelial cells. TM promotes the activation of thrombin-activatable fibrinolysis inhibitor, and also protects cells in blood vessels from inflammation caused by pathogen-associated and damaged cell-associated molecules. Excessive anticoagulant, fibrinolytic, anti-inflammatory, and tissue regenerative effects in the TM-PC pathway are controlled by PC inhibitor. A recombinant TM drug (TM), a soluble form of natural TM developed from the cloned human TM gene, has been evaluated for efficacy in many clinical trials and approved as a treatment for disseminated intravascular coagulation (DIC) caused by diseases such as sepsis, solid tumors, hematopoietic tumors, and trauma. It is currently widely used to treat DIC in Japan.
血栓调节蛋白（TM）是血管内血液凝固、纤维蛋白溶解和炎症的重要调节因子。TM抑制凝血酶的促凝血和促炎活性，并促进凝血酶诱导的与内皮细胞蛋白C受体（EPCR）结合的蛋白C（PC）的活化。活化的蛋白C（APC）使凝血因子Va和VIIIa失活，从而抑制血液凝固。与EPCR结合的APC对血管内皮细胞发挥抗炎和细胞保护作用。TM促进凝血酶激活的纤维蛋白溶解抑制剂的活化，还保护血管中的细胞免受病原体相关和受损细胞相关分子引起的炎症。TM-PC途径中过度的抗凝、纤维蛋白溶解、抗炎和组织再生作用由蛋白C抑制剂控制。一种重组TM药物（TM），是从克隆的人TM基因开发的天然TM的可溶性形式，已在许多临床试验中评估其疗效，并被批准用于治疗由败血症、实体瘤、造血肿瘤和创伤等疾病引起的弥散性血管内凝血（DIC）。目前它在日本被广泛用于治疗DIC。
