Mechanism of small bowel adhesion correlated with fibrynolytic system
Project/Area Number |
16K19956
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
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Research Institution | Juntendo University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | PAI / 癒着 / tPA / イレウス / EGF / 術後 / マクロファージ / 腸閉塞 / 凝固線溶系 / PAI-1 / プラスミン / 腹腔内癒着 / 凝固線溶 |
Outline of Final Research Achievements |
Adhesive small bowel obstruction remains a common problem for surgeons. Fibrin degradation is important by tPA and plasmin. Peritoneal adhesion was induced by gauze deposition and tPA and PAI1 deficient mice were used. Mice were treated with the novel PAI1 inhibitor, TM5275. Some animals were treated with clodronate to deplete macrophages. Epidermal growth factor (EGF) experiments were performed to understand the role of macrophages and how EGF contributes to adhesion.Genetic and pharmacologic PAI1 inhibition prevented progression of adhesion and increased plasmin. PAI1, in combination with tPA, served as a chemoattractant for macrophages that, in turn, secreted EGF and up-regulated the receptor, HER1, on peritoneal mesothelial cells, which led to PAI-1 secretion. Controlled inhibition of PAI-1 not only enhanced activation of the fibrinolytic system, but also prevented recruitment of EGF-secreting macrophages.
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice.2017
Author(s)
Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata M, Takeda K, Sakamoto K, Hattori K, Heissig B.
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Journal Title
The FASEB Journal
Volume: 31
Pages: 2625-2637
Related Report
Peer Reviewed
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[Journal Article] Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice.2017
Author(s)
Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B.
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Journal Title
FASEB Journal
Volume: -
Issue: 6
Pages: 2625-2637
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pharmacological targeting of plasmin prevents lethality and tissue damage in a murine model of macrophage activation syndrome2017
Author(s)
1.Shimazu H, Munakata S, Tashiro Y, Salama Y, Eiamboonser S, Ohta Y, Onoda H, Tsuda Y, Okada Y, Nakauchi H, Heissig B and Hattori K
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Journal Title
Blood
Volume: 印刷中
Issue: 1
Pages: 59-72
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The fibrinolytic pathway expands the murine bone marrow mesenchymal stem/stromal cells through a crosstalk with endothelial cells2016
Author(s)
3.Dhahri D, Sato-Kusubata K, Ohki-Koizumi M, Nishida C, Tashiro Y, Munakata S, Shimazu H, Salama Y, Eiamboonser S, Nakauchi H, Hattori K and Heissig B
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Journal Title
Blood
Volume: 128
Issue: 8
Pages: 1063-1075
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] 当院で経験した大腸癌術後腸閉塞の検討2016
Author(s)
本庄薫平, 河野眞吾, 牧野有里香, 茂木俊介, 塚本亮一, 伊藤慎吾, 盧尚志, 市川亮介, 呉一眞, 宗像慎也, 丹羽浩一郎, 石山隼, 杉本起一, 神山博彦, 高橋玄, 小島豊, 五藤倫敏, 奥澤淳司, 冨木裕一, 坂本一博
Organizer
第71回日本大腸肛門病学会学術集会
Place of Presentation
伊勢
Related Report