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Analysis of wound healing mechanism of neurofibromatosis type I

Research Project

Project/Area Number 18K19615
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionOsaka University

Principal Investigator

KUBO TATEKI  大阪大学, 医学系研究科, 教授 (00362707)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords筋線維芽細胞 / レックリングハウゼン病 / ケロイド
Outline of Final Research Achievements

We found that neurofibromin was implicated in the differentiation of fibroblasts into myofibroblasts in response to mechanical stimulation through the LIMK/cofilin/actin filament dynamics pathway. When neurofibromin was dysfunctional, LIMK and cofilin activation-inactivation chage became less responsive to mechanical stimulation, leading to the stable expression of α-SMA, which induce less scar formation. Thus, this molecular pathway may be a potential therapeutic target for the treatment of itractable hypertrophic scars and keloids.

Academic Significance and Societal Importance of the Research Achievements

レックリングハウゼン病由来線筋維芽細胞に着目することで、neurofibrominより下流の細胞骨格に関するシグナル伝達が、瘢痕形成の原因となる機械的伸展刺激下の筋線維芽細胞への分化誘導に関わることを解明したが、現在まで同様の発表は未だなされておらず、新規のものである。そして、難治であるケロイド・肥厚性瘢痕治療につながるLIMKやcofilinをターゲットとした創薬の可能性を示したことで、今後のscarless wound healingの実現へ一歩前進した。本研究は人類のQOL向上に貢献できうると考える。

Report

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

    (2 results)

All 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-β1 secretion in abnormal scar formation.2019

    • Author(s)
      Maeda D, Kubo T, Kiya K, Kawai K, Matsuzaki S, Kobayashi D, Fujiwara T, Katayama T, and Hosokawa K.
    • Journal Title

      J Plast Surg Hand Surg

      Volume: 53 Pages: 288-294

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurovascular interactions in skin wound healing.2019

    • Author(s)
      Kiya K and Kubo T.
    • Journal Title

      Neurochem Int

      Volume: 125 Pages: 144-150

    • DOI

      10.1016/j.neuint.2019.02.014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed

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Published: 2018-07-25   Modified: 2021-02-19  

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