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Molecular mechanisms of the itch sensation and skin inflammation induced by epidermal tight junction barrier deficiency

Research Project

Project/Area Number 15K15422
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

Kubo Akiharu  慶應義塾大学, 医学部(信濃町), 准教授 (70335256)

Co-Investigator(Renkei-kenkyūsha) KUBO Akiharu  理化学研究所, 統合生命医科学研究センター, チームリーダー (50452272)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsタイトジャンクション / 皮膚バリア / かゆみ / アトピー性皮膚炎 / クローディン1 / 角質バリア / 角質 / クローディン1 / ランゲルハンス細胞 / 皮膚炎
Outline of Final Research Achievements

The stratum corneum (SC) and tight junctions (TJs) form physical barriers in the skin. A congenital TJ barrier defect caused by a deficiency of claudin-1, which encodes a major epidermal TJ adhesion molecule, results in early neonatal death in mice and neonatal ichthyosis-sclerosing cholangitis syndrome in humans. These observations suggest the essential role of TJs in skin homeostasis. Here, we established tamoxifen (TAM)-inducible epidermis-specific claudin-1 knockout mice (K14-creERT+/-, Cldn1flox/flox mice) and investigated the pathophysiology of epidermal TJ defects in adult mice. To clarify the barrier defects of the SC and TJ separately, we measured water evaporation through isolated SC sheets (WETIS) ex vivo.On day 8, claudin-1 staining disappeared, but no elevation of WETIS was observed. On day 18, compact hyperkeratosis and increased WETIS were observed, suggesting that the TJ barrier leakage secondarily induced the SC barrier defect.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2016 2015

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 8 results,  Invited: 4 results)

  • [Journal Article] Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape2016

    • Author(s)
      Yokouchi M, Atsugi T, Logtestijn MV, Tanaka RJ, Kajimura M, Suematsu M, Furuse M, Amagai M, Kubo A
    • Journal Title

      Elife

      Volume: 5

    • DOI

      10.7554/elife.19593

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape2016

    • Author(s)
      Kubo A
    • Organizer
      2nd International Symposium on ‘Autoinflammation breaks Barriers’
    • Place of Presentation
      Munster, Germany
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Spatiotemporal orchestration of epidermal cell turnover based on Kelvin’s tetrakaidecahedron cell shape2016

    • Author(s)
      Kubo A
    • Organizer
      CDB International Symposium “Body Surface Tactics”
    • Place of Presentation
      理化学研究所多細胞システム形成研究センター(兵庫県神戸市中央区)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Homeostasis and Dysfunction of the Epidermal Barriers2016

    • Author(s)
      Kubo A
    • Organizer
      12th Meeting of the German-Japanese Society of Dermatology
    • Place of Presentation
      軽井沢プリンスホテルウエスト(長野県軽井沢市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape2016

    • Author(s)
      Kubo A
    • Organizer
      14th Meeting of the European Epidermal Barrier Research Network
    • Place of Presentation
      Munchen, Germany
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell shape determines the regulatory mechanisms for maintaining tight junction barrier homeostasis in epidermal turnover2016

    • Author(s)
      Yokouchi M, Atsugi T, Kajimura M, Suematsu M, Furuse M, Amagai M, Kubo A
    • Organizer
      76th Annual Meeting Society for Investigative Dermatology
    • Place of Presentation
      Kierland, Arizona, USA
    • Year and Date
      2016-05-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] claudin-1欠損マウスを用いた脂腺タイトジャンクションバリアの解析2016

    • Author(s)
      厚木徹, 横内麻里子, 平林愛, 大山学, 天谷雅行, 久保亮治
    • Organizer
      第23回分子皮膚フォーラム
    • Place of Presentation
      ホテルグランヴィア大阪(大阪府大阪市北区)
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Functional tight junction barriers in sebaceous glands: defects in holocrine secretion in claudin-1 deficient mice2015

    • Author(s)
      Atsugi T, Yokouchi M, Hirabayashi A, Ohyama M, Amagai M, Kubo A
    • Organizer
      The 40 th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epidermis-specific ablation of claudin-1 in adult mice demonstrates a key role of tight junction barrier in the development of atopic dermatitis2015

    • Author(s)
      Kubo A, Hirano T, Kawasaki H, Yokouchi M, Atsugi T, Amagai M
    • Organizer
      The 64th Meeting of Japanese Society of Allergology
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都港区)
    • Year and Date
      2015-05-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tight junction barrier dysfunction induced by epidermis-specific claudin-1 ablation is sufficient to cause dermatitis in mice2015

    • Author(s)
      Kubo A, Hirano T, Yokouchi M, Kawasaki H, Atsugi T, Amagai M
    • Organizer
      75th Annual Meeting Society for Investigative Dermatology
    • Place of Presentation
      アトランタ(USA)
    • Year and Date
      2015-05-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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