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Signaling induced by mechanical stimulation of fluied shear stress in cultured corneal epithelial cells

Research Project

Project/Area Number 16K20295
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionAsahikawa Medical College

Principal Investigator

Utsunomiya Tsugiaki  旭川医科大学, 大学病院, 医員 (50646065)

Research Collaborator Nagaoka Taiji  
Hanada Kazuomi  
Ishii Nobuhito  
Ishibazawa Akihiro  
Matsumoto Chiemi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords角膜上皮細胞 / シェアストレス / TGFB / ドライアイ / 瞬目関連疾患 / 角膜上皮障害 / 角膜 / 瞬目 / 機械的刺激 / ANGPTL / 角膜上皮
Outline of Final Research Achievements

Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs). The HCECs were exposed to shear stress with the parallel-plate type of flow chamber, which exposed the cells to variable levels of laminar shear stress.
Fluid shear stress on the HCECs affected TGF-β signaling, which was associated with delayed wound healing. Mechanical stress by blinking might involve TGF-β signaling, and activation of TGF-β might be a key factor in wound healing of the corneal epithelium. Further studies should investigate the molecular mechanism induced shear stress.

Academic Significance and Societal Importance of the Research Achievements

現在のドライアイ治療は対症療法であり、病態解明に基づいた治療の確立には至っていない。ドライアイ等の眼表面疾患において瞬目による摩擦力の重要性が着目され、瞬目による摩擦力は流体力学的に捉えることが可能である。水流によって培養細胞に定量的に長時間にわたって機械的刺激を負荷する実験手法を培養ヒト角膜上皮細胞に応用し、瞬目の摩擦による角膜上皮への慢性的な機械的刺激を再現、培養ヒト角膜上皮細胞において機械的刺激負荷によってTGF-βのシグナル伝達が活性化されることがわかった。機械的刺激負荷後のシグナル伝達を解析することで、ドライアイ等眼表面疾患の病態解明、新薬開発に寄与す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

    (4 results)

All 2018 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Transforming Growth Factor-β Signaling Cascade Induced by Mechanical Stimulation of Fluid Shear Stress in Cultured Corneal Epithelial Cells.2016

    • Author(s)
      宇都宮嗣了,石羽澤明弘,長岡泰司,花田一臣,横田陽匡,石居信人,吉田晃敏
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 57(14) Issue: 14 Pages: 6382-6388

    • DOI

      10.1167/iovs.16-20638

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 流体力学的アプローチを用いた瞬目時摩擦刺激による角膜上皮細胞のANGPTL4発現上昇2018

    • Author(s)
      宇都宮 嗣了, 石羽澤 明弘, 横山一弘, 松本千恵美, 花田 一臣, 石居信人, 吉田 晃敏
    • Organizer
      第42回日本角膜学会総会/第34回日本角膜移植学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 流体力学的アプローチを用いた瞬目摩擦刺激による角膜上皮細胞のANGPTL4発現上昇2018

    • Author(s)
      宇都宮 嗣了
    • Organizer
      日本角膜学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Effects of mechanical stimulation of fluid shear stress in cultured corneal epithelial cells2016

    • Author(s)
      宇都宮嗣了,石羽澤明弘,長岡泰司,花田一臣,吉田晃敏
    • Organizer
      The Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      シアトル
    • Year and Date
      2016-05-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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

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