Analysis of pleiotropic property of thrombomodulin and development of therapeutic strategy using thrombomodulin in transplantation
| Project/Area Number |
25461942
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Aichi Medical University (2015)
Nagoya University (2013-2014) |
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Principal Investigator |
MIWA YUKO 愛知医科大学, 医学部, 寄附講座 助教 (90572941)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI TAKAAKI 愛知医科大学, 医学部 外科学講座(腎移植外科), 教授 (70314010)
IWASAKI KENTA 愛知医科大学, 医学部 腎疾患・移植免疫学寄附講座, 准教授 (10508881)
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| Co-Investigator(Renkei-kenkyūsha) |
ONISHI AKIRA 日本大学, 生物資源科学部, 教授 (30414890)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 移植・再生医療 / 凝固系制御 / 異種移植 / 移植･再生医療 |
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| Outline of Final Research Achievements |
Thrombomodulin (TM) is a vascular endothelial cell receptor that functions as a cofactor for activated protein C (APC). From the viewpoint of coagulation control using TM in transplantation, two strategy including (i) administration of recombinant soluble thrombomodulin (S-hTM), which has been approved for the treatment of sepsis-induced DIC, and (ii) upregulation of membrane-bound TM (MB-hTM) expression in endothelial cells would be proposed. As a result, S-hTM had more potent capacity of APC production and inhibitory effect on thrombin generation than MB-hTM. In contrast, MB-hTM suppressed the expression of inflammatory factor in endothelial cells. It was speculated that S-hTM treatment would be of assistance during high-risk periods for excessive thrombin formation (e.g., ischemia reperfusion injury or severe infection/rejection). Considering the properties of MB-hTM exhibiting anti-inflammatory function, might be required to long-term stabilization of graft endothelial cells.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in renal transplantation.2014
Author(s)
Kurata Y, Kuzuya T, Miwa Y, Iwasaki K, Haneda M, Amioka K, Yamada K, Watarai Y, Katayama A, Uchida K, Kobayashi K
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Journal Title
International Immunopharmacology
Volume: 22
Issue: 2
Pages: 384-391
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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