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Comprehensive functional analysis of S100 fused-type protein family in skin barrier formation

Research Project

Project/Area Number 18K08265
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionUniversity of Toyama

Principal Investigator

Teruhiko Makino  富山大学, 学術研究部医学系, 准教授 (90359711)

Co-Investigator(Kenkyū-buntansha) 清水 忠道  富山大学, 学術研究部医学系, 教授 (70260396)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsS100 fused-type protein / フィラグリン / アトピー性皮膚炎 / S100 fused-type蛋白質 / 表皮角化細胞 / 皮膚バリア / 角化 / S100 fused-type蛋白質群
Outline of Final Research Achievements

In the present study, we comprehensively examined an association of S100 fused-type protein family, including filaggrin (FLG), filaggrin-2 (FLG2), hornerin (HRNR), trichohyalin (TCHH), trichohyalin like 1 (TCHHL1), repetin (RPTN) and cornulin (CRNN), in the barrier formation in the atopic skin. To induce atopic dermatitis (AD) skin model, 3D skin equivalents were stimulated with recombinant IL-4 and IL-13. In this skin model, expression of FLG and FLG2 were significantly decreased and expression of RPTN and TCHH were significantly increased. On the other hand, expression of FLG, CRNN, TCHHL1 were significantly decreased and expression of FLG2, HRNR and TCHH were significantly increased. These results suggest that a regulation of the expression and a function in the barrier formation in the atopic skin may be different among S100 fused-type protein family members.

Academic Significance and Societal Importance of the Research Achievements

本研究の特色はFLGとそれに類似するS100 fused-type蛋白質群の全ての分子の機能解析を同時に行ったことにある。これにより各分子の皮膚の組織構築への関与を比較検討することが可能となり、ヒト表皮角化細胞を用いた3次元皮膚モデルの解析により、ヒト皮膚における各分子の機能と疾患との関連を直接解明できる。本研究で皮膚のバリア形成において重要な役割を担い、さらにアトピー性皮膚炎と関連しうる分子が同定されつつある。さらに研究が進展すればアトピー性皮膚炎の病態解明のみならず新規治療法の開発にもつながる可能性があり、臨床医学において大きな意味を持つといえる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2021 2020 2019 2018

All Journal Article (17 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 17 results,  Open Access: 9 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Dysregulation of Amphiregulin stimulates the pathogenesis of cystic lymphangioma2021

    • Author(s)
      Yoshida N, Yamamoto S, Hamashima T, Okuno N, Okita N, Horikawa S, Hayashi M, Dang TC, Nguyen QL, Nishiyama K, Makino T, Ishii Y, Tomihara K, Shimizu T, Shibuya M, Noguchi M, Sasahara M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 118 Issue: 19

    • DOI

      10.1073/pnas.2019580118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Development of Solar Elastosis with Increased Expression of Fibrillin-1, LTBP-2 and Fibulin-4 in Combination with Decreased Expression of LTBP-42021

    • Author(s)
      Makino T、Kagoyama K、Murabe C、Nakamura T、Shimizu T
    • Journal Title

      Acta Dermato Venereologica

      Volume: 101 Issue: 1 Pages: adv00372-adv00372

    • DOI

      10.2340/00015555-3738

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful treatment of acne fulminans with the combination of prednisolone and diaminodiphenylsulfone.2021

    • Author(s)
      Furukawa F, Makino T, Mori S, Shimizu T.
    • Journal Title

      J Dermatol.

      Volume: 48 Issue: 2

    • DOI

      10.1111/1346-8138.15699

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repigmentation within hypopigmented lesions of pigmentary mosaicism.2021

    • Author(s)
      Shimizu K, Makino T, Shimizu T.
    • Journal Title

      Clin Exp Dermatol.

      Volume: 46 Issue: 3 Pages: 565-567

    • DOI

      10.1111/ced.14470

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of laminin-5 gamma 2 chain predicts invasion of extramammary Paget's disease cell.2021

    • Author(s)
      Tohmatsu Y, Imura J, Sakai T, Takagi K, Minamisaka T, Tanaka S, Noguchi A, Nakajima T, Nagata T, Makino T, Shimizu T, Fujii T.
    • Journal Title

      APMIS.

      Volume: 129 Issue: 1 Pages: 3-8

    • DOI

      10.1111/apm.13086

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophilic myositis developing in a case of systemic lupus erythematosus.2021

    • Author(s)
      Matsui Y, Makino T, Torai R, Shimizu T.
    • Journal Title

      ur J Dermatol.

      Volume: 30 Issue: 4 Pages: 432-433

    • DOI

      10.1684/ejd.2020.3807

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravascular myopericytoma on the right dorsal foot.2020

    • Author(s)
      Kagoyama K, Makino T, Minamisaka T, Shimizu T.
    • Journal Title

      Eur J Dermatol.

      Volume: 30 Issue: 6 Pages: 736-737

    • DOI

      10.1684/ejd.2020.3906

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trichohyalin-like 1 protein plays a crucial role in proliferation and anti-apoptosis of normal human keratinocytes and squamous cell carcinoma cells2020

    • Author(s)
      Makino Teruhiko、Mizawa Megumi、Yoshihisa Yoko、Yamamoto Seiji、Tabuchi Yoshiaki、Miyai Masashi、Hibino Toshihiko、Sasahara Masakiyo、Shimizu Tadamichi
    • Journal Title

      Cell Death Discovery

      Volume: 6 Issue: 1 Pages: 2020-2020

    • DOI

      10.1038/s41420-020-00344-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation2020

    • Author(s)
      Matsuda, T. Kambe, N. Hosokawa, J. Ohara, O. Saito, M. K. Nishikomori, R.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 79 Issue: 11 Pages: 1492-1499

    • DOI

      10.1136/annrheumdis-2020-217320

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Agminated flexural melanocytic nevus associated with Langerhans cell histiocytosis.2020

    • Author(s)
      Makino T, Matsui Y, Torai R, Mizawa M, Shimizu T.
    • Journal Title

      J Dermatol.

      Volume: 47 Issue: 7

    • DOI

      10.1111/1346-8138.15391

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of pazopanib for local and lung metastases in Stewart-Treves syndrome.2020

    • Author(s)
      Hayashi M, Makino T, Mori N, Mizawa M, Shimizu T.
    • Journal Title

      Eur J Dermatol.

      Volume: 30 Pages: 68-69

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sarcoid reactions in the skin caused by mantle cell lymphoma.2020

    • Author(s)
      Furukawa F, Makino T, Takemoto K, Mizawa M, Arita K, Hamashima T, Shimizu T.
    • Journal Title

      Eur J Dermatol.

      Volume: 30 Pages: 57-58

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultraviolet B irradiation increases the expression of trichohyalin-like 1 protein in human skin xenotransplants.2019

    • Author(s)
      Makino T, Mizawa M, Yoshihisa Y, Shimizu T.
    • Journal Title

      Clin Exp Dermatol

      Volume: 44 Issue: 7 Pages: 773-776

    • DOI

      10.1111/ced.13904

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of itching in mycosis fungoides: grade of itching correlates with eosinophil infiltration and kallikrein 5 expression.2019

    • Author(s)
      Shimizu K, Andoh T, Makino T, Yoshihisa Y, Mizawa M, Shimizu T.
    • Journal Title

      Eur J Dermatol.

      Volume: 29 Pages: 268-273

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Missense mutation Y449H of the K10 gene in a patient with severe epidermolytic ichthyosis.2019

    • Author(s)
      Takemoto K, Makino T, Mizawa M, Kubo Y, Shimizu T.
    • Journal Title

      Eur J Dermatol.

      Volume: 29 Pages: 227-228

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inflammatory cytokine-mediated induction of serine racemase in atopic dermatitis.2018

    • Author(s)
      Yoshihisa Y, Rehman MU, Nakagawa M, Matsukuma S, Makino T, Mori H, Shimizu T.
    • Journal Title

      J Cell Mol Med

      Volume: ー Issue: 6 Pages: 3133-3138

    • DOI

      10.1111/jcmm.13592

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nerve alterations showing autophagy in 2 patients with lichen aureus2018

    • Author(s)
      Yanagihara M、Makino T、Shimizu T、Mochizuki T
    • Journal Title

      Journal of Cutaneous Pathology

      Volume: 印刷中 Issue: 6 Pages: 423-427

    • DOI

      10.1111/cup.13131

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] サルコイドーシスを合併した抗PM-SCL抗体陽性皮膚筋炎2020

    • Author(s)
      牧野輝彦,清水忠道
    • Organizer
      強皮症・膠原病国際シンポジ ウム2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Agminated flexural melanocytic nevus with Langerhans cell histiocytosis.2020

    • Author(s)
      Makino T, Matsui Y, Mizawa M, Shimizu T.
    • Organizer
      第24 回国際色素細胞学会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Trichohyalin-like 1 protein plays a crucial role in the proliferation of normal human keratinocytes and squamous cell carcinoma cells.2020

    • Author(s)
      Makino T, Mizawa M, Yoshihisa Y, Yamamoto S, Tabuchi Y, Miyai M, Shimizu T.
    • Organizer
      第45回日本研究皮膚科 学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エキシマレーザーXTRAC Velocity7による難治性皮膚疾患に対する治療.2020

    • Author(s)
      牧野輝彦
    • Organizer
      第71回日本皮膚科学会中 部支部学術大会
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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