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Impaired function of extracellular matrix 1 alters the fibrogenic and carcinogenic properties: implications of underlying mechanisms for the pathogenesis of lichen sclerosus

Research Project

Project/Area Number 17K16334
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionUniversity of Fukui

Principal Investigator

Utsunomiya Natsuko  福井大学, 学術研究院医学系部門(附属病院部), 医員 (50792090)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords硬化性苔癬 / ECM1 / 自己抗体 / 基底膜 / 皮膚診断学 / 皮膚腫瘍
Outline of Final Research Achievements

Lichen sclerosus (LS) is an acquired inflammatory dermatosis that mainly affects anogenital area. Serum autoantibodies to extracellular matrix protein 1 (ECM1) in patients may hold clues in the underlying pathogenesis of LS. cDNA microarray comparing between ECM1-knockdown and control fibroblasts identified 3,035 differentially expressed genes, which related exclusively to protein binding for cell adhesion and proliferation, apoptosis, intracellular signaling, and extracellular matrix organization. Of these, laminin-332 and collagen-IV displayed unique immunolabeling of the basement membrane zone and dermal vessels in the LS skin by ECM1 knockdown. ECM1-knockdown fibroblasts exhibited a marked delay in cell migration and gel contraction. ECM1 gene silencing may prime selective dysregulation and disassembly of structural and extracellular matrix molecules in fibroblasts, reflecting the microstructural disorganization in LS pathology.

Academic Significance and Societal Importance of the Research Achievements

本研究では、抗体を指標とした硬化性苔癬の血清診断ならびに病勢把握ツールの開発に向けた臨床応用の可能性を追求しながら、患者血清中に存在する抗ECM1抗体の病的意義の解明を目指した。ヒト線維芽細胞を用いてECM1を特異的に発現を低下させると連動する線維化と癌化に関与する遺伝子を同定した。これらの成果は、硬化性苔癬の分子特異的な病態のさらなる真相解明に直結し、本症の早期診断や患者の生命予後を改善させる知見へと繋がる可能性が高いと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Journal Article] Dietary supplement product composed of natural ingredients as a suspected cause of erythema multiforme: a case report and identification for the confident false-positivity of lymphocyte transformation test.2019

    • Author(s)
      Natsuko Utsunomiya
    • Journal Title

      Journal of Dermatology

      Volume: 46 Issue: 3 Pages: 234-239

    • DOI

      10.1111/1346-8138.14739

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Impaired function of ECM1 underlies the pathogenic disorganization of vascular and basement membrane molecules in lichen sclerosus2019

    • Author(s)
      Natsuko Utsunomiya
    • Organizer
      49th Annual ESDR Meeting 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Detection of serum autoantibodies to extracellular matrix protein 1 (ECM1) and relevant abnormal expression of hemidesmosomal antigens in lichen sclerosus2018

    • Author(s)
      Natsuko Utsunomiya
    • Organizer
      International Investigative Dermatology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Circulating IgG autoantibodies to ECM1 contribute to the altered expression of hemidesmosomal and vascular antigens in lichen sclerosus skin2017

    • Author(s)
      Natsuko Utsunomiya
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Serodiagnostic utility and in vivo expression profile of hemidesmosomal antigens in lichen sclerosus: a confocal laser scanning immunofluorescence microscopic study2017

    • Author(s)
      Natsuko Utsunomiya
    • Organizer
      2017 Annual Meeting-Society For Investigative Dermatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] ミドリムシ製剤服用後に発症した多形紅斑の1例―薬剤リンパ球刺激試験(DLST)の偽陽性についてー2020

    • Author(s)
      宇都宮 夏子
    • Total Pages
      3
    • Publisher
      秀潤社
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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