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学科主题: 基础医学
题名:
Cartilage oligomeric matrix protein is a natural inhibitor of thrombin
作者: Liang, Ying1,2; Fu, Yi1,2; Qi, Ruomei3,4; Wang, Meili1,2; Yang, Nan1,2; He, Li1,2; Yu, Fang1,2; Zhang, Jian5; Yun, Cai-Hong6; Wang, Xian1,2; Liu, Junling7; Kong, Wei1,2
刊名: BLOOD
发表日期: 2015-08-13
DOI: 10.1182/blood-2015-01-621292
卷: 126, 期:7, 页:905-914
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology
研究领域[WOS]: Hematology
关键词[WOS]: THROMBOSPONDIN-1 ; DISEASE ; MICE ; PROTEOMICS ; RECEPTORS ; ADAMTS-7 ; ADHESION ; BINDS ; COMP
英文摘要:

Thrombin is an effector enzyme for hemostasis and thrombosis; however, endogenous regulators of thrombin remain elusive. Cartilage oligomeric matrix protein (COMP), a matricellular protein also known as thrombospondin-5, is essential for maintaining vascular homeostasis. Here, we asked whether COMP is involved in the process of blood coagulation. COMP deficiency shortened tail-bleeding and clotting time and accelerated ferric-chloride-induced thrombosis in mice. The absence of COMP had no effect on platelet count. In contrast, COMP specifically inhibited thrombin-induced platelet aggregation, activation, and retraction and the thrombin-mediated cleavage of fibrinogen. Furthermore, surface plasmon resonance analysis revealed direct thrombin-COMP binding (K-D = 1.38 +/- 0.24 mu M). In particular, blockage of thrombin exosites with compounds specific for exosite I (hirudin and HD1 aptamer) or exosite II (heparin and HD22 aptamer) impaired the COMP-thrombin interaction, indicating a 2-site binding mechanism. Additionally, epidermal growth factor-like repeats (amino acids 84-261) were identified as a COMP binding site for thrombin. Moreover, COMP was expressed in and secreted by platelets. Using bone marrow transplantation and platelet transfusion to create chimeric mice, platelet-derived but not vessel-wall-derived COMP was demonstrated to inhibit coagulation. Taken together, COMP is an endogenous thrombin inhibitor and negative regulator of hemostasis and thrombosis.

语种: 英语
所属项目编号: 81220108004 ; 2012CB518002 ; 81070243 ; 81121061 ; 91339000 ; 81225002 ; B07001 ; 81300198
项目资助者: International Cooperation and Exchanges NSFC ; National Program on Key Basic Research Project (973 Program) ; National Natural Science Foundation of People&prime ; s Republic of China ; National Science Fund for distinguished Young Scholars ; "111" Project of Chinese Ministry of Education ; National Science Fund for Young Scholars
WOS记录号: WOS:000360530800014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63443
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Minist Educ, Beijing Inst Geriatr, Beijing, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
3.Minist Educ, Beijing Hosp, Key Lab Geriatr, Beijing, Peoples R China
4.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol, Shanghai 200030, Peoples R China
6.Peking Univ, Sch Basic Med Sci, Dept Biophys, Beijing 100191, Peoples R China
7.Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai, Peoples R China

Recommended Citation:
Liang, Ying,Fu, Yi,Qi, Ruomei,et al. Cartilage oligomeric matrix protein is a natural inhibitor of thrombin[J]. BLOOD,2015,126(7):905-914.
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