2015 Fiscal Year Final Research Report
Studies in the action mechanism of fibrinolytic system on the inflammatory bowel disease and its clinical applications
| Project/Area Number |
25461961
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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 | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Koichi 順天堂大学, 医学部, 特任先任准教授 (10360116)
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| Co-Investigator(Renkei-kenkyūsha) |
HEISSIG Beate 東京大学, 医科学研究所, 准教授 (30372931)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 炎症性大腸炎 / クローン病 / IBD / 血液線維素溶解系 / マトリックスメタロプロテアーゼ / 好中球エラスターゼ / プラスミン / 炎症性サイトカイン |
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| Outline of Final Research Achievements |
We previously verified inflammatory bowel diseases (IBD) was suppressed by fibrinolytic system inhibitors in mice. In this study, we aimed to clarify functions of fibrinolytic system in development of IBD. Circulating levels of plasmin were higher in mice with colitis than in control mice. Colitis did not develop in mice injected with plasmin inhibitors or with plasminogen-binding proteins. Colons dissected from these mice had been reduced infiltration of Gr1+ neutrophil and F4/80+ macrophage, and reduced levels of inflammatory cytokines and chemokines. We also found that activation of endogenous MMP9 leads colonic inflammation. Moreover, application of neutrophil elastase inhibitor improved therapeutic conditions of IBD in the mice. These results suggested that the disruption of chronic inflammatory circuit by inhibition of fibrinolysis factors should be an effective method for IBD treatment.
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| Free Research Field |
消化器外科学
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