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Development of a new theraphy for keloids with inhibition of HtrA1 and a new keloid organ culture system

Research Project

Project/Area Number 15H05003
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Naitoh Motoko  国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 客員研究員 (30378723)

Co-Investigator(Kenkyū-buntansha) 江野尻 竜樹  京都大学, 医学研究科, 助教 (00748270)
山脇 聖子  京都大学, 医学(系)研究科(研究院), 客員研究員 (70378777)
吉川 勝宇  京都大学, 医学研究科, 助教 (10583156)
Co-Investigator(Renkei-kenkyūsha) KUBOTA Hiroshi  秋田大学, 工学資源学部, 教授 (80332724)
SUZUKI Shigehiko  京都大学, 医学研究科, 教授 (30187728)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywordsケロイド / 創傷治癒 / 動物モデル / HtrA1 / マトリックス / ケロイドモデル / 再生医学 / 細胞・組織 / 組織培養 / 創傷治癒学 / セリンプロテアーゼ / モデル動物
Outline of Final Research Achievements

Although we could not establish a keloid organ culture system, we developed a novel keloid model using an unique nude mice and thechnique to implant keloid tissues into mice.Keloid fibroblasts treated with HtrA1 siRNA exhibited a proliferation rate significantly slower. This effect with silencing HtrA1 was also observed in normal fibroblasts, but the inhibition effect was not as pronounced. We could not confirmed this effect on our novel keloid model.However, our results could contribute to investigation of keloid pathogenesis and new treatments.

Academic Significance and Societal Importance of the Research Achievements

HtrA1は、ケロイドが拡大していく辺縁部に特に強く発現しており、ケロイド由来細胞を増殖させることが示された。HtrA1の働きを阻害するとケロイド由来細胞の増殖が抑制されることから、ケロイド治療ターゲットとして期待できる。本研究では、この効果を検証するための新規ケロイドモデルの作成も試みた。その結果、免疫不全マウスにケロイド組織を移植固定する技法を開発し、従来より病態を反映する新規ケロイドモデル作成に成功した。ケロイド組織の特徴を維持するケロイドモデルが作成できたことは、ケロイドの病態解明や治療薬開発に大いに貢献するものと期待できる。

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (12 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] HtrA1 Is Specifically Up-Regulated in Active Keloid Lesions and Stimulates Keloid Development.2018

    • Author(s)
      Yamawaki S, Naitoh M, Kubota H, Aya R, Katayama Y, Ishiko T, Tamura T, Yoshikawa K, Enoshiri T, Ikeda M, Suzuki S.
    • Journal Title

      Int J Mol Sci.

      Volume: 19(5) Issue: 5 Pages: 1275-1275

    • DOI

      10.3390/ijms19051275

    • NAID

      120006510299

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-Adrenergic Receptor Blockers Reduce the Occurrence of Keloids and Hypertrophic Scars after Cardiac Device Implantation: A Single-Institution Case-Control Study.2017

    • Author(s)
      Enoshiri T, Naitoh M, Yamawaki S, Kawaguchi A, Aya R, Noda K, Katayama Y, Doi T, Kawaji T, Suzuki S.
    • Journal Title

      Plast Reconstr Surg.

      Volume: 139 Issue: 5 Pages: 1248-1256

    • DOI

      10.1097/prs.0000000000003239

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ケロイド・肥厚性瘢痕の保存的治療とエコーによる評価2016

    • Author(s)
      綾 梨乃, 山脇 聖子, 内藤 素子, 鈴木 茂彦
    • Journal Title

      PEPARS

      Volume: 117 Pages: 8-12

    • Related Report
      2016 Annual Research Report
  • [Journal Article] The Shear Wave Velocity on Elastography Correlates with the Clinical Symptoms and Histopathological Features of Keloids.2015

    • Author(s)
      Aya R, Yamawaki S, Yoshikawa K, Katayama Y, Enoshiri T, Naitoh M, Suzuki S.
    • Journal Title

      Plast Reconstr Surg Glob Open.

      Volume: 3(7) Issue: 7 Pages: e464-e464

    • DOI

      10.1097/gox.0000000000000445

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 超音波診断機器を用いたケロイド・瘢痕の評価2017

    • Author(s)
      山脇聖子、内藤素子、綾梨乃、片山康博、江野尻竜樹、齊藤晋、鈴木茂彦
    • Organizer
      第9回創傷外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] コンドロイチナーゼに着目した新規ケロイド治療薬の開発2017

    • Author(s)
      内藤素子、山脇聖子、片山泰博、綾梨乃、石河利広、池田美香、江野尻竜樹、片岡和哉、鈴木茂彦
    • Organizer
      第47回日本創傷治癒学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ケロイド移植モデルの構築(第一報)2017

    • Author(s)
      池田実香・松添晴加・内藤素子・片岡和哉・セ 也・豊島公栄・辻孝
    • Organizer
      第26回日本形成外科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ケロイド・肥厚性瘢痕に置ける神経の局在2017

    • Author(s)
      松添晴加・池田実香・内藤素子・片岡和哉・セ 也・豊島公栄・辻孝
    • Organizer
      第26回日本形成外科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ケロイド・肥厚性瘢痕に置ける神経の局在2017

    • Author(s)
      池田実香・松添晴加・内藤素子・片岡和哉・セ 也・豊島公栄・辻孝
    • Organizer
      第12回瘢痕・ケロイド治療研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Up-regulation of HtrA1 in keloid tissues.2016

    • Author(s)
      Satoko Yamawaki, Motoko Naitoh, Toshihiro Ishiko, Katsuhiro Yoshikawa, Tatsuki Enoshiri, Rino Aya, Yasuhiro Katayama, Shigehiko Suzuki
    • Organizer
      The 5th World Congress of the World Union of Wound Healing Societies
    • Place of Presentation
      Fortezza da Basso, Florence, Italy
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Our strategy for the keloid treatments2016

    • Author(s)
      Yamawaki S, Naitoh M, Katayama Y, Aya R, Enoshiri T, Noda K, Suzuki S
    • Organizer
      The 13th Japan-Korea Congress of Plastic and Reconstructive Surgery
    • Place of Presentation
      ANAクラウンプラザホテル金沢
    • Year and Date
      2016-05-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Quantitative assessment of scar stiffness using ultrasonography2015

    • Author(s)
      Yamawaki S, Naitoh M, Aya R, Katayama Y, Enoshiri T, Saitoh S, Suzuki
    • Organizer
      7th joint meeting of Europearn Tissue Repair Society and the Wound Healing Society
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2021-01-27  

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