Elucidation of the relationship between the platelet receptor CLEC-2 and the pathophysiology of sepsis and its application as a new therapeutic target
Project/Area Number |
17K16185
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Hematology
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Research Institution | University of Yamanashi |
Principal Investigator |
SASAKI Tomoyuki 山梨大学, 大学院総合研究部, 准教授 (40739124)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | CLEC-2 / 血小板 / 敗血症 / 好中球 / NETs |
Outline of Final Research Achievements |
In the present study, we used a mouse model of sepsis and a model of neutrophil NETs formation to elucidate the role of the platelet-activated receptor CLEC-2 in the pathogenesis of sepsis. As a result, the survival rate due to platelet CLEC-2 expression in the sepsis model differed in the induction method. Induction by appendectomy significantly prolonged survival with CLEC-2 deficiency, but no difference was observed with LPS administration. In neutrophil NETs formation, co-culture with LPS and platelets induced NETs formation and was further inhibited by CLEC-2 blockers. This indicates that platelet CLEC-2 contributes to the formation of neutrophil NETs, which are involved in innate immunity.
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Academic Significance and Societal Importance of the Research Achievements |
血小板CLEC-2の病態生理学的役割は,血小板血栓の形成のみならず,血栓の安定化,癌の転移に寄与することが報告されていたが,敗血症との関連は不明であった.本研究において,血小板CLEC-2が敗血症と好中球のNETs形成に寄与することが示唆された.そのメカニズムなどのさらなる解析を進める必要はあるが,血小板CLEC-2が抗血小板効果と抗NETs形成効果の両者によって敗血症性DICへの新たな治療標的となる可能性がある.
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Report
(4 results)
Research Products
(24 results)
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[Presentation] An inhibitory mutant of snake venom rhodocytin blocks CLEC-2/Podoplanin interaction dependent platelet aggregation and experimental lung metastasis.2017
Author(s)
Sasaki T, Shirai T, Tsukiji N, Otake S, Tamura S, Osada M, Satoh K, Ozaki Y, Suzuki-Inoue K
Organizer
ISTH 2017 Congress, Berlin, Germany. (July 8-13 2017)
Related Report
Int'l Joint Research
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