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Molecular mechanisms for the epidermal barrier homeostasis

Research Project

Project/Area Number 26293259
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 佐々木 貴史  慶應義塾大学, 医学部, 講師 (70306843)
天谷 雅行  慶應義塾大学, 医学部, 教授 (90212563)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywordsタイトジャンクション / 皮膚バリア / 組織恒常性 / 形と機能 / 表皮 / ケルビン14面体 / 表皮恒常性 / アレルギー / 遺伝子 / 免疫学 / 発生・分化 / 各層 / ターンオーバー / 上皮組織 / 表皮角化 / 重層上皮細胞 / 単層上皮細胞
Outline of Final Research Achievements

In multicellular organisms, cells adopt various shapes, from flattened sheets of endothelium to dendritic neurons, that allow the cells to function effectively. Here, we elucidated the unique shape of cells in the stratified epithelia of the epidermis that allows them to achieve homeostasis of the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that the basic shape of TJ-bearing cells is a flattened Kelvin’s tetrakaidecahedron (f-TKD), an optimal shape for filling space. In vivo live imaging further elucidated the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ-bearing cells to translocate across the TJ barrier. We propose a spatiotemporal orchestration model of f-TKD cell turnover, where in the classic context of “form follows function,” cell shape provides a fundamental basis for the barrier homeostasis and physical strength of cornified stratified epithelia.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (32 results)

All 2016 2015 2014 Other

All Int'l Joint Research (4 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 13 results,  Invited: 13 results) Remarks (4 results)

  • [Int'l Joint Research] Imperial College of London(United Kingdom)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Emory University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ケルン大学(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] インペリアルカレッジ・ロンドン(英国)

    • Related Report
      2015 Annual Research Report
  • [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
  • [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
  • [Presentation] Epidermal barrier homeostasis and its breakage in skin diseases2016

    • Author(s)
      Kubo A
    • Organizer
      10th Annual Symposium in Institute of Human-Environment Interface Biology
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2016-02-20
    • Related Report
      2015 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
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [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
    • 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)
    • 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)
    • 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
      2nd International Symposium on ‘Autoinflammation breaks Barriers’
    • Place of Presentation
      Munster, Germany
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epidermal barrier homeostasis and its breakage in skin diseases2016

    • Author(s)
      Kubo A
    • Organizer
      The 41st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      仙台国際センター(宮城県仙台市青葉区)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Homeostatic cell turnover mechanisms that maintain tight junction barrier integrity in the epidermis.2015

    • Author(s)
      Yokouchi M, Kajimura M, Suematsu M, Furuse M, Amagai M, and Kubo A
    • Organizer
      The 6th Annual Congress of Pan AsianPacific Skin Barrier Research Society PAPSBRS
    • 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
      2015-12-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Homeostatic cell turnover mechanisms that maintain tight junction barrier integrity in the epidermis2015

    • Author(s)
      Yokouchi M, Kajimura M, Suematsu M, Furuse M, Amagai M, and 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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Classical cadherins control polarized organization of junctions and cytoskeleton in stratified epithelia2015

    • Author(s)
      Rubsam M, Kubo A, Mertz A, Boggetti B, Goranci G, Dufresne E, Horsley V, Amagai M, and Niessen C
    • 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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional tight junction barriers in sebaceous glands: defects in holocrine secretion in claudin-1 deficient mice.2015

    • Author(s)
      Atsugi T, Yokouchi M, Hirabayashi A, Ohyama M, Amagai M, and 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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Vicious Cycle in Atopic Dermatitis: Epidermal Barriers, Allergic Sensitization and Inflammation2015

    • Author(s)
      Kubo A
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市白石区)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tight junctions, the skin barrier and atopic dermatitis2015

    • Author(s)
      Kubo A
    • Organizer
      23rd World Congress of Dermatology
    • Place of Presentation
      バンクーバー(カナダ)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [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 homeostasis2014

    • 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
      Kyoto
    • Year and Date
      2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Tight junction barriers in the skin and skin diseases2014

    • 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] Ishizaki I, Miyayama T, Sanada N, Kubo A, and Setou M2014

    • Author(s)
      Ishizaki I, Miyayama T, Sanada N, Kubo A, and Setou M
    • Organizer
      SISS-16 (The Scientific International Symposium on SIMS and Related Techniques Based on Ion-Solid Interactions)
    • Place of Presentation
      Sapporo
    • Year and Date
      2014-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Tight junction barriers are functionally organized in hair follicles and sebaceous glands.2014

    • Author(s)
      Atsugi T, Yokouchi M, Ohyama M, Amagai M, and 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
  • [Remarks] Sealing the deal on leak-proof cells

    • URL

      https://research-highlights.keio.ac.jp/article/82/sealing-the-deal-on-leak-proof-cells

    • Related Report
      2016 Annual Research Report
  • [Remarks] 皮膚が新陳代謝しつつバリアを維持する仕組みを解明 -細胞の形が解き明かす瑞々しい皮膚が保たれる秘密-

    • URL

      https://www.keio.ac.jp/ja/press-releases/files/2016/11/30/161130_2.pdf

    • Related Report
      2016 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
      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

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Published: 2014-04-04   Modified: 2022-02-16  

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