2017 Fiscal Year Final Research Report
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 |
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| Research Field |
Digestive surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | PAI / 癒着 / tPA / イレウス / EGF |
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| 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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| Free Research Field |
消化器外科
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