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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| 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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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 / 炎症性腸疾患 / マトリックスメタロプロテイナーゼ / 線維素溶解系 / プラスミン阻害剤 / TNFα / 潰瘍性大腸炎 |
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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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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Impact of chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis2016
Author(s)
Kawai M, Komiyama H, Hosoya M, Okubo H, Fujii T, Yokoyama, N, Sato C, Ueyama T, Okuzawa A, Goto M, Kojima Y, Takahashi, M Sugimoto K, Ishiyama S, Munakata S, Ogura D, Niwa S, Tomiki Y, Ochiai T, Sakamoto K.
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Journal Title
Oncology Letters
Volume: 11
Related Report
Peer Reviewed
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[Journal Article] Inhibition of Plasmin Protects Against Colitis in Mice by Suppressing Matrix Metalloproteinase 9-Mediated Cytokine Release From Myeloid Cells.2015
Author(s)
Munakata S, Tashiro Y, Nishida C, Sato A, Komiyama H, Shimazu H, Dhahri D, Salama Y, Eiamboonsert S, Takeda K, Yagita H, Tsuda Y, Okada Y, Nakauchi H, Sakamoto K, Heissig B, Hattori K.
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Journal Title
Gastroenterology
Volume: 148
Issue: 3
Pages: 565-78
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Investigation of free cancer cells in peripheral blood using CEA mRNA expression in perioperative colorectal cancer patients.2013
Author(s)
Nagayasu K, Komiyama H, Ishiyama S, Ogura D, Takahashi R, Tashiro Y, Niwa K, Sugimoto K, Kojima Y, Goto M, Tomiki Y, Niwa S, Sakamoto K.
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Journal Title
Molecular and clinical oncology
Volume: 1
Issue: 4
Pages: 668-674
DOI
Related Report
Peer Reviewed
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[Presentation] Comparisons of long-term outcomes for locally advanced colon cancer between laparoscopic colectomy and open colectomy; propensity score analysis2015
Author(s)
Sugimoto K, Sakamoto K, Tomiki Y, Goto M, Kojima Y, Komiyama H, Takahashi M, Kamiyama H, Ishiyama S, Niwa K, Ito S, Kawai M, Takehara K, Tashiro T, Munakata S, Aoki J, Okazawa Yu O, Takahashi R, Mizukoshi K, Ro H, Ichikawa R, Kure K, Honjyo K, Tsukamoto R.
Organizer
23th International Congress of the EAES
Place of Presentation
Bucharest, Romania
Year and Date
2015-06-03
Related Report
Int'l Joint Research
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[Presentation] CHFR methylation is an independent prognostic marker of poor prognosis in gastric cancer:2015
Author(s)
Sugimoto K, Humbert A, Lu Z, Chen C, Rodgers K, Lee,B Griffin C, Sato K, Orita H, Ito T, Komiyama H, Kojima Y, Goto M, Tomiki Y, Sakamoto K, Brock M
Organizer
2015 American Association for Cancer Research Annual Meeting
Place of Presentation
Pennsylvania, USA
Year and Date
2015-04-18
Related Report
Int'l Joint Research
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[Presentation] 腹腔内癒着における線溶系阻害因子PAI-1の機能解明2015
Author(s)
本庄薫平, 塚本亮一, 植山孝恵, 伊藤慎吾, 市川亮介, 呉一眞, 盧尚志, 田代良彦, 宗像慎也, 高橋玄, 小見山博光, 小島豊, 五藤倫敏, 冨木裕一, 市村敦彦, 段孝, 宮田敏男, Beate Heissig, 服部浩一, 坂本一博
Organizer
第115回日本外科学会定期学術集会
Place of Presentation
名古屋
Year and Date
2015-04-16
Related Report
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