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Determination of the functions of specific CD44 proteins in human skin and epidermis and their relation to skin diseases, cancer and autoimmunity

Research Project

Project/Area Number 16K10137
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionKurume University

Principal Investigator

TEYE Kwesi  久留米大学, 付置研究所, 助教 (30599303)

Co-Investigator(Kenkyū-buntansha) 橋本 隆  久留米大学, 皮膚細胞生物学研究所, 教授 (20129597)
名嘉真 武国  久留米大学, 医学部, 教授 (50221453)
沼田 早苗  久留米大学, 医学部, 助教 (40599312)
石井 文人  久留米大学, 医学部, 准教授 (80330827)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsCD44 / Skin / Skin disease / Keratinocyte / Squamous cell carcinoma / migration / Human Skin Keratinocyte / Skin Cancer / Human Skin / 皮膚生理 / 生物学
Outline of Final Research Achievements

We studied functions and roles of CD44 proteins in human skin. We for the first time identified 18 transcripts of CD44 in epidermal keratinocytes and studied their roles in skin development. To gain insight into CD44 function, we performed immunostaining of normal skin and various skin diseases. We found decreased expression of CD44 variants in various skin cancers, particularly squamous cell carcinoma but not in inflammatory diseases psoriasis and atopic dermatitis. Using CRISPR/Cas9 system, we successfully disrupted CD44 expression in keratinocyte cell line and performed Microarray analysis using RNA from cells with and without CD44. We found that expression of many important genes are controlled by CD44. Importantly, we found that expression of all 3 subunits of a certain laminin, which is important for maintaining structural integrity of human skin, are reduced in cells without CD44. Cells without CD44 migrated slower. Our study revealed important functions of CD44 in human skin.

Academic Significance and Societal Importance of the Research Achievements

CD44の皮膚での役割はよく分かっていない。本研究ではCD44の発現が有棘細胞癌で減少していること、CD44の発現をなくした表皮細胞において、皮膚の構造を保つ上で重要な働きをするラミニンの3つのサブユニットの発現がすべて減少していることを明らかにした。またCD44を有さない表皮細胞は移動が遅くなることも明らかにした。以上の結果からCD44は創傷治癒において重要な役割を果たしている可能性が示唆された。CD44はある種の皮膚疾患において、治療の標的になり得るかもしれない。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(14 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Detection of anti‐type VII collagen IgE antibodies in epidermolysis bullosa acquisita2019

    • Author(s)
      Koga H.、Teye K.、Yamashita K.、Ishii N.、Tsuruta D.、Nakama T.
    • Journal Title

      British Journal of Dermatology

      Volume: 180(5) Issue: 5 Pages: 1107-1113

    • DOI

      10.1111/bjd.17310

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical and Immunological Study of 30 Cases With Both IgG and IgA Anti-Keratinocyte Cell Surface Autoantibodies Toward the Definition of Intercellular IgG/IgA Dermatosis2018

    • Author(s)
      Hashimoto Takashi、Teye Kwesi、Hashimoto Koji、Wozniak Katarzyna、Ueo Daisuke、Fujiwara Sakuhei、Inafuku Kazuhiro、Kotobuki Yorihisa、Jukic Ines Lakos、Marinovi? Branka、Bruckner Anna、Tsuruta Daisuke、Kawakami Tamihiro、Ishii Norito
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 994-994

    • DOI

      10.3389/fimmu.2018.00994

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High Index Values of Enzyme-Linked Immunosorbent Assay for BP180 at Baseline Predict Relapse in Patients With Bullous Pemphigoid.2018

    • Author(s)
      Koga H, Teye K, Ishii N, Ohata C, Nakama T
    • Journal Title

      Front Med (Lausanne)

      Volume: 5 Pages: 1-5

    • DOI

      10.3389/fmed.2018.00139

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The haptoglobin promoter polymorphism rs5471 is the most definitive genetic determinant of serum haptoglobin level in a Ghanaian population.2018

    • Author(s)
      Soejima M, Teye K, Koda Y.
    • Journal Title

      Clin Chim Acta.

      Volume: 483 Pages: 303-307

    • DOI

      10.1016/j.cca.2018.05.029

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multimerization is required for antigen binding activity of an engineered IgM/IgG chimeric antibody recognizing a skin-related antigen2017

    • Author(s)
      Teye K, Hashimoto K, Numata S, Ohta K, Haftek M, Hashimoto T
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 8212-8212

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of SERPINB7 mutation can distinguish Nagashima-type palmoplantar keratoderma from other keratodermas with palmoplantar lesions2017

    • Author(s)
      Hashimoto T, Teye K, Numata S, Suga Y, Hamada T, Ishii N
    • Journal Title

      Clinical and Experimental Dermatology

      Volume: 42 Pages: 324-325

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prevalence of filaggrin gene mutations in patients with atopic dermatitis and ichthyosis vulgaris in Kyushu area of Japan and South Korea2017

    • Author(s)
      Teye K, Numata S, Krol RP, Ishii N, Matsuda M, Lee JB, Hamada T, Hashimoto T
    • Journal Title

      Journal of Dermatological Science

      Volume: 86 Pages: 174-177

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid2017

    • Author(s)
      Hashimoto T, Ohzono A, Teye K, Numata S, Hiroyasu S, Tsuruta D, Hachiya T, Kuroda K, Hashiguchi M, Kawakami T, Ishii N
    • Journal Title

      Br J Dermatology

      Volume: 177(1) Pages: 141-151

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isolation of All CD44 Transcripts in Human Epidermis and Regulation of Their Expression by Various Agents.2016

    • Author(s)
      Kwesi Teye, Sanae Numata, Norito Ishii, Rafal P. Krol, Atsunari Tsuchisaka, Takahiro Hamada, Hiroshi Koga, Tadashi Karashima, Chika Ohata, Daisuke Tsuruta, Hideyuki Saya, Marek Haftek, Takashi Hashimoto
    • Journal Title

      PLoS ONE

      Volume: 11(8) Issue: 8 Pages: e0160952-e0160952

    • DOI

      10.1371/journal.pone.0160952

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Unusual CD44 form in epidermal differentiation.2019

    • Author(s)
      Kwesi Teye, Hiroshi Koga, Norito Ishii, Sanae Numata, Takashi Hashimoto, Marek Haftek, Takekuni Nakama,
    • Organizer
      Gordon Research Conference (GRC) on Barrier Function of Mammalian Skin.(Waterville Valley, NH, USA, August 11 - 16, 2019)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Filaggrin gene (FLG) promoter polymorphisms are associated with atopic dermatitis but not ichthyosis vulgaris.2018

    • Author(s)
      Kwesi Teye, Hiroshi Koga, Akira Nagai, Chika Ohata, Sanae Numata, Norito Ishii, and Takekuni Nakama.
    • Organizer
      第25回分子皮膚科学フォーラム, Hakodate,(April 13-14, 2018)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Filaggrin gene (FLG) promoter polymorphisms are associated with atopic dermatitis but not ichthyosis vulgaris in Japan,2018

    • Author(s)
      Kwesi Teye, Hiroshi Koga, Akira Nagai, Chika Ohata, Sanae Numata, Norito Ishii and Takekuni Nakama,
    • Organizer
      IID2018, Orlando, Florida,(May 16-19, 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multimerization is required for antigen binding activity of an engineered IgM/IgG chimeric antibody recognizing a skin-related antigen2017

    • Author(s)
      Teye K, Hashimoto K, Numata S, Ohta K, Haftek M, Hashimoto T
    • Organizer
      42st Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of CD44 transcripts that segregate with proliferation, redox and differentiation activities in human keratinocytes.2016

    • Author(s)
      Kwesi Teye, Sanae Numata, Norito Ishii, Koga Hiroshi, Daisuke Tsuruta, Hideyuki Saya, Marek Haftek, Takashi Hashimoto.
    • Organizer
      43rd Annual SCUR Meeting
    • Place of Presentation
      Lyon, France.
    • Year and Date
      2016-08-29
    • 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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