Molecular mechanism elucidation of alternative fibrin degradation pathway aiming for diagnosis and treatment of plasminogen deficiency
| Project/Area Number |
15K09449
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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 |
Hematology
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
ICHINOSE Akitada 山形大学, 名誉教授 (10241689)
SOURI Masayoshi 山形大学, 医学部, 准教授 (20292419)
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| Research Collaborator |
SUZUKI Takashi
IKEWAKI Junko
SONG Young-Seok
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | プラスミノゲン欠乏症 / FDP / 質量分析 / モノクロ－ナル抗体 / プロテアーゼ / ELISA / モノクローナル抗体 |
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| Outline of Final Research Achievements |
We concentrated fibrin degradation products (FDP) by its specific antibodies and identified cleavage sites of FDP, followed by a estimation of candidate proteases which cleave the cleavage sites. As a result, plasmin (PLM), cathepsin G, granulocyte elastase and matrix metalloproteinase-3 were considered candidates. We investigated the fibrin degradation by these proteases. The fibrin degradations in patients were mainly due to residual PLM activity, corresponding to about 15% of the degradations in healthy controls, while the degradations were little affected by other proteases. On the other hand, we found that the specific complement system proteins were high levels in the patient by plasma proteome analysis. Therefore, we investigated the complement activity on a fibrin clot. We found that the complement system was activated on the fibrin clot. We postulated that the complement-opsonized fibrin clot might be removed by phagocytosis.
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Report
(4 results)
Research Products
(4 results)
