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The development and application of in vivo evaluation of mucosal barrier function in functional gastrointestinal disorders

Research Project

Project/Area Number 16K09297
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionHyogo Medical University

Principal Investigator

OSHIMA Tadayuki  兵庫医科大学, 医学部, 准教授 (00381814)

Co-Investigator(Kenkyū-buntansha) 三輪 洋人  兵庫医科大学, 医学部, 教授 (80190833)
渡 二郎  兵庫医科大学, 医学部, 教授 (10311531)
福井 広一  兵庫医科大学, 医学部, 准教授 (60378742)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords機能性消化管疾患 / 細胞間接着装置 / タイト結合 / クローディン
Outline of Final Research Achievements

To assess gastrointestinal barrier function in functional gastrointestinal disorders and controls, the probe that can measure admittance was inserted through the working channel of upper gastroduodenal endoscopy. The probe was attached on the mucosa and admittance was measured. Esophageal admittance was lower than gastric or duodenal admittance, indicating the mucosal barrier function is higher in esophagus compared to stomach or duodenum.
Claudin 1 and claudin 4 were important for the mucosal barrier function of esophageal, but the amount of the expression did not mean the barrier function, and claudins stained as dots and whisker like lines in the granular layers were important for the barrier function. Infiltration of duodenal mucosal mast cells and eosinophils were more at the second portion of duodenum in FD patients compared to controls.

Academic Significance and Societal Importance of the Research Achievements

消化管は粘膜上皮によって体内と体外を分け,体内への異物侵入を制御する重要な機能を担っているが,種々の疾患でこのバリア機能が障害される病態が指摘されている.しかし,このバリア機能異常を客観的に評価する方法は限られ,簡便な検査法の開発が望まれている.本研究では,その簡便な検査法として内視鏡下にプローブを挿入することで消化管粘膜のバリア機能を評価する手法の確立を目指した.消化管の各臓器で生理的な粘膜バリア機能が異なることが明らかとなり,種々の病態でこのバリア機能の障害があることが明らかとなった.今後この測定法が,多くの病態における消化管機能検査として有用な新たな検査法となることが期待される.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 8 results,  Invited: 6 results) Book (1 results)

  • [Journal Article] Duodenal low-grade inflammation and expression of tight junction proteins in functional dyspepsia2019

    • Author(s)
      Taki M, Oshima T, Li M, Sei H, Tozawa K, Tomita T, Fukui H, Watari J, Miwa H
    • Journal Title

      Neurogastroenterology & motility

      Volume: Epub ahead Issue: 10

    • DOI

      10.1111/nmo.13576

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center2019

    • Author(s)
      Miwa H, Oshima T, Tomita T, Fukui H, Kondo T, Yamasaki T, Watari J
    • Journal Title

      Journal of gastroenterology

      Volume: 54 Issue: 4 Pages: 305-311

    • DOI

      10.1007/s00535-019-01550-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Dyspepsia - A Revolution in Management2018

    • Author(s)
      Oshima T, Miwa H
    • Journal Title

      American journal of gastroenterology

      Volume: 113 Issue: 10 Pages: 1420-1422

    • DOI

      10.1038/s41395-018-0264-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Filaggrin and tight junction proteins are crucial for IL-13-mediated esophageal barrier dysfunction2018

    • Author(s)
      Wu L, Oshima T, Li M, Tomita T, Fukui H, Watari J, Miwa H.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 315 Issue: 3 Pages: G341-G350

    • DOI

      10.1152/ajpgi.00404.2017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 機能性ディスペプシアにおける十二指腸微細炎症(Duodenal microinflammation in functional dyspepsia)2019

    • Author(s)
      大島忠之,滝 正登,清 裕生,堀川知紀,Li Min,西井謙夫,富田寿彦,福井広一,渡 二郎,三輪洋人
    • Organizer
      第15回日本消化管学会総会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Relationship between bile acids and low-grade inflammation of small intestine in IBS2019

    • Author(s)
      Horikawa T, Oshima T, Li M, Kondo T, Kono T, Tozawa K, Tomita T, Fukui H, Watari J, Miwa H
    • Organizer
      The 12th International Gastrointestinal Consensus Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胃食道逆流症の病態と治療2019

    • Author(s)
      大島忠之
    • Organizer
      第15回日本消化管学会総会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Functional GI disorders and microbiota2018

    • Author(s)
      Oshima T
    • Organizer
      The 2nd Seoul International Symposium on Helicobacter and Upper Gastrointestinal Diseases
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Stress and impaired gastric accommodation in functional dyspepsia2018

    • Author(s)
      Oshima T
    • Organizer
      Summer School on Stress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ストレスを考慮した機能性ディスペプシア/胃食道逆流症合併患者の診療2018

    • Author(s)
      大島忠之
    • Organizer
      第20回日本神経消化器病学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] CDCA released proinflammatory cytokine from small intestinal epithelial cells2018

    • Author(s)
      Horikawa T, Oshima T, Li M, Kondo T, Kono T, Tozawa K, Tomita T, Fukui H, Watari J, Miwa H
    • Organizer
      3rd Meeting of the Federation of Neurogastroeterology and Motility Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Epithelial barrier dysfunction and immunomodulation in eosinophilic esophagitis2018

    • Author(s)
      Oshima T
    • Organizer
      The 7th Cross-strait Digestive Disease Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Low-grade inflammation and epithelial junctional proteins of duodenal mucosa in functional dyspepsia2017

    • Author(s)
      Masato Taki, Tadayuki Oshima, Kumiko Nakamura, Mayu Takimoto, Akio Tamura, Ken Hara, Masaya Kobayashi, Takuya Okugawa, Tomoaki Kono, Katsuyuki Tozawa, ToshihikoTomita, Yoshio Ohda, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
    • Organizer
      ANMA & JSNM Joint Meeting 2017
    • Place of Presentation
      Osaka International Convention Center (大阪府大阪市)
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The duodenum, a new target for research2017

    • Author(s)
      Tadayuki Oshima, Masato Taki, Liping Wu, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
    • Organizer
      ANMA & JSNM Joint Meeting 2017
    • Place of Presentation
      Osaka International Convention Center (大阪府大阪市)
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Duodenal low-grade inflammation and tight junction proteins in functional dyspepsia.2017

    • Author(s)
      Taki M, Oshima T, Takimoto M, Nakamura K, Tamura A, Hara K, Kobayashi M, Okugawa T, Kono T, Tozawa K, Tomita T, Taniguchi Y, Ohda Y, Fukui H, Watari J, Miwa H.
    • Organizer
      Digestive Disease Week 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] Functional dyspepsia2019

    • Author(s)
      Oshima T, Miwa H
    • Total Pages
      187
    • Publisher
      Springer Nature
    • ISBN
      9789811310737
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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