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Molecular mechanism of luminal pressure reception and ATP release in gastrointestinal epithelium

Research Project

Project/Area Number 26870214
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Gastroenterology
Research InstitutionUniversity of Toyama

Principal Investigator

Mihara Hiroshi  富山大学, 大学院医学薬学研究部(医学), 助教 (00612623)

Co-Investigator(Renkei-kenkyūsha) NISHIZONO Hirofumi  富山大学, 研究推進機構 研究推進総合支援センター, 助教 (10502289)
SUGIYAMA Toshiro  富山大学, 大学院医学薬学研究部(医学), 教授 (00196768)
TOMINAGA Makoto  大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 教授 (90260041)
TABUCHI Yoshiaki  富山大学, 研究推進機構 研究推進総合支援センター, 教授 (20322109)
WATANABE Shiro  富山大学, 和漢医薬学総合研究所, 准教授 (00222406)
UCHIDA Kunitoshi  福岡歯科大学, 歯学部, 講師 (20581135)
KOIZUMI Schuichi  山梨大学, 総合研究部, 教授 (10280752)
Research Collaborator Boudaka Ammar  
YAMAWAKI Hidemoto  
SUZUKI Nobuhiro  
Muhammad Jibran Sualeh  
KOZAWA Toyomi  
Fujinami Haruka  
ANDO Takayuki  
NANJO Sohachi  
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords消化管上皮 / 伸展刺激 / ATP放出 / TRPV4 / VNUT / 胃 / ATP / 伸展 / メチル化 / 結腸 / 上皮細胞
Outline of Final Research Achievements

Approximately 15% of Japanese people have chronic abdominal pain of unknown origin and hypersensitivity to gastrointestinal pressure is one of possible causes. The esophagus senses a tension with mechano-sensitive TRPV4 ion channel and releases bag-like adenosine triphosphate (ATP) using its transporter (VNUT). As a result of the study, TRPV4 and VNUT are present not only in the esophagus but also from the stomach to the rectum, and ATP is released via VNUT by TRPV4 stimulation, including stretch stimuli. Mice lacking TRPV4 have gastric motor abnormality and Helicobacter pylori infection decreases TRPV4 (gene methylation). It has also succeeded in quantifying the TRPV4 stimulating component synthesized in the gastrointestinal tract and so the possibility of quantifying invisible abdominal pain has come out.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (17 results)

All 2018 2017 2016 2015 2014 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] 消化管上皮の圧受容と慢性炎症2018

    • Author(s)
      三原 弘
    • Journal Title

      北隆館BIO Clinica

      Volume: 33 Pages: 46-51

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 消化管上皮の圧受容と慢性炎症2017

    • Author(s)
      三原 弘
    • Journal Title

      北隆館別冊BIO Clinica

      Volume: 6 Pages: 117-122

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium2017

    • Author(s)
      Hiroshi Mihara, Nobuhiro Suzuki, Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa,Toshiro Sugiyama
    • Journal Title

      Helicobacter

      Volume: 22 Issue: 2

    • DOI

      10.1111/hel.12361

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia2016

    • Author(s)
      Mihara H, Sugiyama , et al.
    • Journal Title

      World J Gastroenterol.

      Volume: 22 Issue: 24 Pages: 5512-5519

    • DOI

      10.3748/wjg.v22.i24.5512

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Protease-Activated Receptor-2 Up-Regulates Transient Receptor Potential Vanilloid 4 Function in Mouse Esophageal Keratinocyte.2015

    • Author(s)
      Suzuki N, Mihara H, Nishizono H, Tominaga M, Sugiyama T.
    • Journal Title

      Dig Dis Sci.

      Volume: 60 Issue: 12 Pages: 3570-8

    • DOI

      10.1007/s10620-015-3822-6

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集 消化器疾患の病態生理H.Pylori 感染胃粘膜における TRPV4 メチル化.2015

    • Author(s)
      三原 弘、杉山 敏郎.
    • Journal Title

      Progress in Medicine (ライフ・サイエンス)

      Volume: 35 Pages: 431-433

    • Related Report
      2015 Research-status Report
  • [Journal Article] H.pylori感染症と胃運動異常.機能性消化管障害の病態と治療.2014

    • Author(s)
      三原 弘
    • Journal Title

      消化器内科

      Volume: 58 Pages: 184-8

    • Related Report
      2014 Research-status Report
  • [Journal Article] Role of transient receptor potential vanilloid 4 activation in indomethacin-induced intestinal damage2014

    • Author(s)
      Yamawaki H., Mihara H., Suzuki N., Nishizono H., Uchida K., Watanabe S., Tominaga M., Sugiyama T.
    • Journal Title

      Am. J. Physiol. Gastrointest. Liver Physiol.

      Volume: 307 Issue: 1 Pages: G33-G40

    • DOI

      10.1152/ajpgi.00105.2013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 機能性ディスペプシアにおけるTRPV4の関与2018

    • Author(s)
      三原弘、杉山敏郎
    • Organizer
      第 14 回日本消化管学会総会学術集会 コアシンポジウム 3 「消化管機能性疾患の新展開」 -機能性ディスペプシアの病態・標的分子―
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] A mechanosensitive ion channel, TRPV4-methylation silencing in gastric epithelium2017

    • Author(s)
      Hiroshi Mihara, Nobuhiro Suzuki, Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa, Toshiro Sugiyama
    • Organizer
      Congress of the Asian Neurogastroenterology and Motility Association
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] H. pylori infection directly induces methylation silencing of a gastric epithelial mechano-sensor, Transient Receptor Potential Vanilloid 4 in gastric epithelial cells2016

    • Author(s)
      Hiroshi Mihara, Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Toshiro Sugiyama
    • Organizer
      Digestive Disease Week 2016
    • Place of Presentation
      San Diego, California United States of America
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gastrointestinal epithelia could be luminal sensors for chemical, hypo osmolality, acid, temperature and stretch via ATP release.2015

    • Author(s)
      Mihara Hiroshi, Sualeh Muhammad Jibran, Suzuki Nobuhiro, Tabuchi Yoshiaki, Sugiyama Toshiro
    • Organizer
      Digestive Disease Week 2015
    • Place of Presentation
      Washington DC
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 化合物,低浸透圧,酸,伸展,温度の各種刺激により胃上皮細胞から放出されたATPが胃内の情報を神経に伝達しうる.2014

    • Author(s)
      三原 弘,Muhammad JS,鈴木庸弘,杉山敏郎,田渕圭章.
    • Organizer
      第7回Japan-Functional Dyspepsia research society(J-FD研究会)
    • Place of Presentation
      東京
    • Year and Date
      2014-11-08
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] TRPV4 活性化による胃上皮細胞からのATP 放出機構の破綻が,H. pylori 関連ディスペプシアの一因になり得る.2014

    • Author(s)
      三原 弘,鈴木庸弘、Muhammad JS,山脇秀元,安藤孝将,藤浪 斗,細川 歩,杉山敏郎
    • Organizer
      第16回日本神経消化器病学会,第8回機能性ディスペプシア研究会,第82回消化器心身医学研究会,第4回IBS研究会 合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] What is the role of TRPV4 expressed in gastric epithelium?2014

    • Author(s)
      Mihara H, Suzuki N, Ando T, Tominaga M, Sugiyama T.
    • Organizer
      The 2nd International Symposium on Mechanobiology (ISMB 2014)
    • Place of Presentation
      岡山
    • Year and Date
      2014-05-20 – 2014-05-23
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] ニュースリリース

    • URL

      https://www.u-toyama.ac.jp/education/news/2016/1011.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 富山大学学術情報リポジトリToRepo

    • URL

      https://toyama.repo.nii.ac.jp/?page_id=32

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2019-03-29  

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