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Evaluation of the tight junction barrier impairment in the pathogenesis of atopic dermatitis

Research Project

Project/Area Number 25670507
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, 講師 (70335256)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥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 / アトピー性皮膚炎 / アレルギー / 角質バリア / バリア破綻 / 角層バリア / 皮膚バリア機能
Outline of Final Research Achievements

The stratum corneum (SC) and tight junctions (TJs) form physical barriers in the skin. Impairment of SC and/or TJ barriers has been reported in atopic dermatitis skin, however, the direct consequence of TJ barrier dysfunction on dermatitis onset is unknown. In this study, we established tamoxifen (TAM)-inducible epidermis-specific claudin-1–knockout mice and investigated the pathophysiology of primary epidermal TJ defects in adult mice.
TJ leakage was initially observed focally on day 4 after TAM injection, and had developed fully on day 8. By contrast, the elevation of transepidermal water loss (TEWL) commenced later, on day 10, and reached its peak by day 18. The dermatitis phenotype, including erythema with scales, also became apparent on day 18. Water evaporation through the isolated SC sheets was normal on day 8 but significantly increased on day 18. Therefore, SC barrier impairment and TEWL elevation were secondarily induced after TJ leakage in this mouse model.

Report

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

    (23 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (14 results) (of which Invited: 11 results) Remarks (4 results)

  • [Journal Article] Epidermal tight junction barrier function is altered by skin inflammation, but not by filaggrin-deficient stratum corneum.2015

    • Author(s)
      Yokouchi M, Kubo A, Kawasaki H, Yoshida K, Ishii K, Furuse M, Amagai M.
    • Journal Title

      J Dermatol Sci.

      Volume: 77 Issue: 1 Pages: 28-36

    • DOI

      10.1016/j.jdermsci.2014.11.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis2014

    • Author(s)
      Yoshida K, Kubo A, Fujita H, Yokouchi M, Ishii K, Kawasaki H, Nomura T, Shimizu H, Kouyama K, Ebihara T, Nagao K, Amagai M.
    • Journal Title

      The Journal of Allergy and Clinical Immunology

      Volume: 134(4) Issue: 4 Pages: 856-864

    • DOI

      10.1016/j.jaci.2014.08.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional tight junction barrier localizes in the second layer of the stratum granulosum of human epidermis2013

    • Author(s)
      Yoshida K, Yokouchi M, Nagao K, Ishii K, Amagai M, Kubo A
    • Journal Title

      J Dermatol Sci

      Volume: 71 Issue: 2 Pages: 89-99

    • DOI

      10.1016/j.jdermsci.2013.04.021

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The stratum corneum comprises three layers with distinct metal-ion barrier properties2013

    • Author(s)
      Kubo A, Ishizaki I, Kubo A, Kawasaki H, Nagao K, Ohashi Y, Amagai M
    • Journal Title

      Sci. Rep

      Volume: 3 Issue: 1 Pages: 1731-1731

    • DOI

      10.1038/srep01731

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 3D visualization of epidermal langerhans cells2013

    • Author(s)
      Kubo, A.
    • Journal Title

      Methods Mol Biol

      Volume: 961 Pages: 119-127

    • DOI

      10.1007/978-1-62703-227-8_5

    • ISBN
      9781627032261, 9781627032278
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 皮膚バリアの構造と機能を可視化する ~バリア破綻疾患の病態解明へのアプローチ~2014

    • Author(s)
      久保亮治
    • Organizer
      第14回医学生物学電子顕微鏡シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-12-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Epidermis-specific ablation of claudin-1 in adult mice demonstrates the essential role of a tight junction barrier in skin homeostasis.2014

    • Author(s)
      Hirano T, Yokouchi M, Atsugi T, Amagai M, and Kubo A.
    • Organizer
      The 39th Annual Meeting of the Japanese Society for Investigative Dermatology,
    • Place of Presentation
      京都
    • Year and Date
      2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Tight junction barriers in the skin and skin diseases.2014

    • Author(s)
      Kubo A.
    • Organizer
      5th Pan Asian Pacific Skin Barrier Research Annual Symposium
    • Place of Presentation
      Tainan, Taiwan
    • Year and Date
      2014-11-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 経皮感作とアレルギー疾患2014

    • Author(s)
      久保亮治
    • Organizer
      第16回日本褥瘡学会学術集会,
    • Place of Presentation
      名古屋
    • Year and Date
      2014-08-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 進化と疾患が教えてくれる皮膚バリア構造の「かたち」と機能2014

    • Author(s)
      久保亮治
    • Organizer
      第41回皮膚かたち研究学会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 角層の形成機構と先天性角層バリア破綻疾患2014

    • Author(s)
      久保亮治
    • Organizer
      第113回日本皮膚科学会総会
    • Place of Presentation
      京都
    • Year and Date
      2014-05-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Tight junction barriers are functionally organized in hair follicles and sebaceous glands2014

    • Author(s)
      Atsugi T, Yokouchi M, Ohyama M, Amagai M, Kubo A.
    • Organizer
      74th Annual Meeting Society for Investigative Dermatology
    • Place of Presentation
      New Mexico, USA
    • Year and Date
      2014-05-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] アトピー性皮膚炎と皮膚バリア2014

    • Author(s)
      久保亮治
    • Organizer
      第77回日本皮膚科学会東京支部
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] The stratum corneum comprises three layers with distinct barrier properties to metal ions2013

    • Author(s)
      Kubo A, Ishizaki I, Kubo A, Kawasaki H, Nagao K, Ohashi Y, and Amagai M
    • Organizer
      International Investigative Dermatology
    • Place of Presentation
      Edinburgh, UK
    • Related Report
      2013 Research-status Report
  • [Presentation] The Three Musketeers of the Epidermal Barrier2013

    • Author(s)
      Kubo A
    • Organizer
      4th Pan Asian Pacific Skin Barrier Research Annual Symposium
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Molecular Barriology of the Stratum Corneum and Epidermal Tight Junctions2013

    • Author(s)
      Kubo A
    • Organizer
      Molecular Mechanisms Regulating Skin Homeostasis 2013
    • Place of Presentation
      Koln, Germany
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 角質層バリアと皮膚免疫2013

    • Author(s)
      久保亮治
    • Organizer
      第29回日本皮膚悪性腫瘍学会学術大会
    • Place of Presentation
      甲府
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] バリア異常からみたアトピー性皮膚炎の病態と治療2013

    • Author(s)
      久保亮治
    • Organizer
      第112回日本皮膚科学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 皮膚タイトジャンクションバリアから見た皮膚疾患の病態と病理.2013

    • Author(s)
      久保亮治
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 久保 亮治 - 常勤スタッフ一覧 - 医療従事者のみなさま - 慶應義塾大学病院 皮膚科

    • URL

      http://www.derma.med.keio.ac.jp/derma/medic/staff/06.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 皮膚バリア機構解明プロジェクト - 実績・研究プロジェクト - 慶應義塾大学病院 皮膚科

    • URL

      http://www.derma.med.keio.ac.jp/derma/medic/project/04.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 久保 亮治 - 常勤スタッフ一覧 - 医療従事者のみなさま - 慶應義塾大学病院 皮膚科

    • URL

      http://www.derma.med.keio.ac.jp/derma/medic/staff/06.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 皮膚バリア機構解明プロジェクト

    • URL

      http://www.derma.med.keio.ac.jp/derma/medic/project/04.html

    • Related Report
      2013 Research-status Report

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

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