凝血调节素-血管内凝血和炎症的关键调节因子,以及弥散性血管内凝血的治疗方法。

IF 4.4 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2024-12-18 DOI:10.2183/pjab.101.006
Koji Suzuki
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引用次数: 0

摘要

凝血调节素(Thrombomodulin, TM)是血管内凝血和炎症的重要调节因子。TM可抑制凝血酶的促凝和促炎活性,并促进凝血酶诱导的结合内皮PC受体(EPCR)的蛋白C (PC)的活化。活化的PC (APC)使凝血因子Va和viia失活,从而抑制血液凝固。此外,与EPCR结合的APC对血管内皮细胞具有抗炎和细胞保护作用。TM还可以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。在TM-PC通路中过度的抗凝血、抗炎和组织再生作用由PC抑制剂控制。重组TM药物(TMα)是一种从克隆的人类TM基因中提取的天然TM的可溶性形式,已经在许多临床试验中进行了疗效评估,并被批准用于治疗脓毒症、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)。目前在日本广泛用于治疗DIC。
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Thrombomodulin - A key regulator of intravascular blood coagulation and inflammation, and a treatment for disseminated intravascular coagulation.

Thrombomodulin (TM) is an important regulator of intravascular blood coagulation 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. Additionally, APC bound to EPCR exerts anti-inflammatory and cytoprotective effects on vascular endothelial cells. TM also protects cells in blood vessels from inflammation caused by pathogen-associated and damaged cell-associated molecules. Excessive anticoagulant, anti-inflammatory, and tissue regenerative effects in the TM-PC pathway are controlled by PC inhibitor. A recombinant TM drug (TMα), 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.

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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: The Proceedings of the Japan Academy Ser. B (PJA-B) is a scientific publication of the Japan Academy with a 90-year history, and covers all branches of natural sciences, except for mathematics, which is covered by the PJA-A. It is published ten times a year and is distributed widely throughout the world and can be read and obtained free of charge through the world wide web.
期刊最新文献
Chemical biology research in RIKEN NPDepo aimed at agricultural applications. First English article of Yagi-Uda antenna. Genome-wide changes of protein translation levels for cell and organelle proliferation in a simple unicellular alga. Mechanisms of autophagosome formation. Thrombomodulin - A key regulator of intravascular blood coagulation and inflammation, and a treatment for disseminated intravascular coagulation.
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