Clearance mechanism of ADAMTS13
Project/Area Number |
16K08515
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | National Cardiovascular Center Research Institute |
Principal Investigator |
Akiyama Masashi 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30298179)
|
Co-Investigator(Kenkyū-buntansha) |
小亀 浩市 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40270730)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | ADAMTS13 / クリアランス機構 / クリアランス受容体 / 蛋白質 / LRP1 / Ashwell-Morell受容体 |
Outline of Final Research Achievements |
The plasma metalloprotease, ADAMTS13 specifically cleaves VWF and negatively regulate platelet thrombus formation. We identified human SIGLEC5 as a clearance receptor candidate. SIGLEC5 expressing HEK293 cells internalized full-length and C-terminal region-deficient ADAMTS13. ADAMTS13 bound extracellular region of SIGLEC5 in vitro. Hydrodynamic-expression human SIGLEC5 in mouse liver lowered plasma Adamts13 activity. These results suggests that SIGLEC5 is involved in the clearance of ADAMTS13.
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Academic Significance and Societal Importance of the Research Achievements |
遺伝子変異もしくは阻害抗体によるADAMTS13活性の著減は重篤な血栓性疾患である血栓性血小板減少性紫斑病(TTP)の病因である。また、ADAMTS13投与はVWFの切断を通じ脳卒中など様々な血栓性疾患モデルマウスにおいて病態を緩和する作用を持つことも明らかになっている。現在先天性TTP患者に組換えADAMTS13製剤を投与し治療する第三相試験が行われている。ADAMTS13のクリアランス機構の解明は投与した組換えADAMTS13の安定性などの改良にも役立つとともに、様々な血栓性疾患の病態改善にも役立つ可能性がある。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] von Willebrand factor aggravates hepatic ischemia-reperfusion injury by promoting neutrophil recruitment in mice2018
Author(s)
Urisono Y, Sakata A, Matsui H, Kasuda S, Ono S, Nishio K, Sho M, Okuchi K, Akiyama M, Miyata T, Nishimura S, Sugimoto M
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Journal Title
Thromb Haemost
Volume: 118
Issue: 04
Pages: 700-708
DOI
Related Report
Peer Reviewed
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[Journal Article] Journal Club2016
Author(s)
秋山正志、小亀浩市
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Journal Title
Japanese Journal of Thrombosis and Hemostasis
Volume: 27
Issue: 3
Pages: 384-385
DOI
NAID
ISSN
0915-7441, 1880-8808
Related Report
Peer Reviewed
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[Presentation] Asymptomatic dysprothrombinemia (Prothtombin Himi) with p.M380T and p.R431H shows severely reduced clotting activity, moderate antithrombin resistance and severe thrombomodulin binding defect.2016
Author(s)
1)Eriko Morishita, Mao Takata, Fumina Taniguchi , Masashi Akiyama, Akiko Sekiya, Akira Takagi, Toshiyuki Miyata, and Tetsuhito Kojima
Organizer
58th ASH Annual Meeting & Exposition
Place of Presentation
San Diego, CA, USA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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