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Mechanism of small bowel adhesion correlated with fibrynolytic system

Research Project

Project/Area Number 16K19956
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionJuntendo University

Principal Investigator

Munakata Shinya  順天堂大学, 医学部, 助教 (50758761)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
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)
KeywordsPAI / 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.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (3 results)

  • [Journal Article] Pharmacological targeting of neutrophil serine proteases prevents lethality in dextran sulfate sodium (DSS)-induced colitis in mice2018

    • Author(s)
      Ro H, Munakata S, Ueyama T, Komiyama H, Takahashi M, Kojima Y, Tomiki Y, Sakamoto K
    • Journal Title

      Journal of Gastrointestinal & Digestive System

      Volume: 8 Issue: 01 Pages: 551-551

    • DOI

      10.4172/2161-069x.1000551

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophil-lymphocyte ratio as a prognostic factor in incurable stage IV colorectal cancer.2018

    • Author(s)
      Munakata S, Sugimoto K, Honjo K, Kawai M, Kawano S, Kamiyama H, Ouchi M, Takahashi M, Tomiki Y, Sakamoto K.
    • Journal Title

      Open Journal of Gastroenterology

      Volume: 8(02) Issue: 02 Pages: 45-56

    • DOI

      10.4236/ojgas.2018.82005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      The FASEB Journal

      Volume: 31 Pages: 2625-2637

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [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.
    • Journal Title

      FASEB Journal

      Volume: - Issue: 6 Pages: 2625-2637

    • DOI

      10.1096/fj.201600871rr

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Blood

      Volume: 印刷中 Issue: 1 Pages: 59-72

    • DOI

      10.1182/blood-2016-09-738096

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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
    • Journal Title

      Blood

      Volume: 128 Issue: 8 Pages: 1063-1075

    • DOI

      10.1182/blood-2015-10-673103

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 炎症性腸疾患におけるプロテアーゼの機能解明2016

    • Author(s)
      宗像慎也,植山孝恵,牧野有里香,本庄薫平,青木 順,高橋里奈,丹羽浩一郎,石山 隼,杉本起一,神山博彦,高橋 玄,柳沼行宏,小見山博光,小島 豊,五藤倫敏,冨木裕一,坂本一博,服部浩一,Beate Heissig
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Related Report
      2016 Research-status Report
  • [Presentation] The risk factor of early postoperative small bowel obstruction (ESBO) after laparoscopic assisted colectomy (LAC)2016

    • Author(s)
      Kumpei Honjo, Kazuhiro Sakamoto, Michitoshi Goto, Koichiro Niwa, Shinya Munakata, Rina Takahashi, Yu Okazawa, Hisashi Ro, Shingo Kawano, Yurika Makino
    • Organizer
      第71回日本消化器外科学会総会
    • Place of Presentation
      徳島
    • Related Report
      2016 Research-status Report
  • [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
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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