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Search for mechanosensors underlying pathophysiology of respiratory diseases

Research Project

Project/Area Number 25461188
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNagoya University

Principal Investigator

Ito Satoru  名古屋大学, 医学部附属病院, 病院講師 (60378073)

Co-Investigator(Kenkyū-buntansha) HASEGAWA Yoshinori  名古屋大学, 大学院医学系研究科, 教授 (20270986)
Co-Investigator(Renkei-kenkyūsha) Sokabe Masahiro  名古屋大学, 大学院医学系研究科, 特任教授 (10093428)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメカニカルストレス / リモデリング / 気管支喘息 / 肺線維症 / カルシウムイオン / 気道平滑筋 / 肺線維芽細胞 / ATP / 細胞伸展 / 血管内皮 / 肺損傷
Outline of Final Research Achievements

This study was designed to investigate effects of mechanical stress on cellular functions of airway smooth muscle cells and lung fibroblasts and the underlying mechanisms of mechanically induced cellular properties.
We found that ATP is released from airway smooth cells in response to mechanical stretch. We successfully visualized mechanically induced ATP releases from individual cells. ATP released from airway smooth muscle cells in response to mechanical stretch may regulate homeostasis of the airway physiology and play a role in the pathophysiology of asthma and COPD.
We also found that mechanical stretch activates the Ca2+ influx pathway independently of the actin cytoskeleton and released ATP in human lung fibroblasts. Our findings suggest that Ca2+ influx in response to mechanical stress would play a role in the progression of pulmonary fibrosis via activating lung fibroblasts.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2016 2015 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) (of which Invited: 3 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Respiratory mechanics measured by forced oscillation technique in rheumatoid arthritis-related pulmonary abnormalities: frequency-dependence, heterogeneity and effects of smoking.2016

    • Author(s)
      Sokai R, Ito S, Iwano S, Uchida A, Aso H, Kondo M, Ishiguro N, Kojima T, Hasegawa Y.
    • Journal Title

      SpringerPlus

      Volume: 5 Issue: 1 Pages: 335-335

    • DOI

      10.1186/s40064-016-1952-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 講座「研究手法入門:薬理生理」機械的ストレス実験2015

    • Author(s)
      伊藤理、長谷川好規.
    • Journal Title

      呼吸

      Volume: 34 Pages: 793-798

    • Related Report
      2015 Annual Research Report
  • [Journal Article] [Review] Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodeling.2014

    • Author(s)
      Noble PD, Pascoe CD, Bo L, Ito S, Kistemaker LE, Tatler AL, Pera T, Brook BS, Gosens R, West AR.
    • Journal Title

      Pulm Pharmacol Ther

      Volume: 29 Issue: 2 Pages: 96-107

    • DOI

      10.1016/j.pupt.2014.07.005

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts.2014

    • Author(s)
      Murata N, Ito S, Furuya K, Takahara N, Naruse K, Aso H, Kondo M, Sokabe M, and Hasegawa Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 453 Issue: 1 Pages: 101-105

    • DOI

      10.1016/j.bbrc.2014.09.063

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Real-Time Imaging of ATP Release Induced by Mechanical Stretch in Human Airway Smooth Muscle Cells.2014

    • Author(s)
      Takahara N, Ito S, Furuya K, Naruse K, Aso H, Kondo M, Sokabe M, and Hasegawa Y
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 51 Issue: 6 Pages: 772-782

    • DOI

      10.1165/rcmb.2014-0008oc

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Influence of cheek support on respiratory impedance measured by forced oscillation technique.2013

    • Author(s)
      Uchida A, Ito S, Matsubara H, Suki B, Hasegawa Y.
    • Journal Title

      SpringerPlus

      Volume: 2 Issue: 1 Pages: 342-342

    • DOI

      10.1186/2193-1801-2-342

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集/咳と痰のサイエンス:気道平滑筋の病態と咳.2013

    • Author(s)
      伊藤理
    • Journal Title

      The LUNG perspectives

      Volume: 21 Pages: 338-342

    • Related Report
      2013 Research-status Report
  • [Presentation] 気道リモデリングの機序と分子標的2016

    • Author(s)
      伊藤理
    • Organizer
      第56回日本呼吸器学会学術講演会(シンポジウム講演)
    • Place of Presentation
      京都府京都市 国立京都国際会館
    • Year and Date
      2016-04-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 肺のメカノバイオロジー:基質硬度による肺線維芽細胞の活性化2016

    • Author(s)
      浅野周一、伊藤理、高橋光太、村田直彦、近藤征史、長谷川好規
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      京都府京都市 国立京都国際会館
    • Year and Date
      2016-04-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺線維芽細胞のメカノバイオロジー:基質硬さによる制御機構2015

    • Author(s)
      伊藤理
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京都千代田区 東京国際フォーラム
    • Year and Date
      2015-04-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mechanobiology of lung fibroblasts: Ca2+ influx and ATP release mediated by mechanical stretch2015

    • Author(s)
      Ito S
    • Organizer
      第55回日本呼吸器学会学術講演会 (English Poster Discussion)
    • Place of Presentation
      東京千代田区 東京国際フォーラム
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Effects of mechanical stretch on intracellular Ca2+ concentrations in human lung fibroblasts.2014

    • Author(s)
      Murata N, Ito S, Hasegawa Y.
    • Organizer
      7th World Congress of Biomechanics 2014
    • Place of Presentation
      Boston, USA.
    • Year and Date
      2014-07-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Mechanics of airway smooth muscle cells.2014

    • Author(s)
      Ito S, Hasegawa Y.
    • Organizer
      7th World Congress of Biomechanics 2014
    • Place of Presentation
      Boston, USA.
    • Year and Date
      2014-07-08
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Effects of mechanical stresses on airway smooth muscle functions.2014

    • Author(s)
      Ito S, Hasegawa Y.
    • Organizer
      International Symposium on Mechanobiology 2014
    • Place of Presentation
      岡山県、岡山市、岡山大学医学部
    • Year and Date
      2014-05-23
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Stretch-activated Ca2+ influx in human lung fibroblasts.2014

    • Author(s)
      Murata N, Ito S, Takahara N, Furuya K, Sokabe M, Hasegawa Y.
    • Organizer
      International Symposium on Mechanobiology 2014
    • Place of Presentation
      岡山県、岡山市、岡山大学医学部
    • Year and Date
      2014-05-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Real-time imaging of mechanical stress-induced ATP release in airway smooth muscle cells.

    • Author(s)
      Ito S, Takahara N, Furuya K, Sokabe M, Hasegawa Y.
    • Organizer
      8th Young Investigator Symposium on Airway Smooth Muscle and Fibroblast Biology.
    • Place of Presentation
      Groningen, the Netherland
    • Related Report
      2013 Research-status Report
  • [Book] DOJIN BIOSCIENCEシリーズ「メカノバイオロジー」2015

    • Author(s)
      伊藤理. (曽我部正博編)
    • Total Pages
      332
    • Publisher
      化学同人
    • Related Report
      2015 Annual Research Report
  • [Book] Calcium signaling in airway smooth muscle cells.2014

    • Author(s)
      Ito S
    • Total Pages
      469
    • Publisher
      Springer
    • Related Report
      2013 Research-status Report
  • [Remarks] 名古屋大学大学院医学系研究科呼吸器内科学

    • URL

      http://www.med.nagoya-u.ac.jp/medical/6391/6393/kokyuukinaikagaku.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] Respiratory Medicine, Nagoya University

    • URL

      http://www.med.nagoya-u.ac.jp/english01/6489/6559/Respiratory-Medicine.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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