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IQGAP1 regulates extracellular matrix remodeling

Research Project

Project/Area Number 20K18488
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionTokyo Dental College

Principal Investigator

Nakajima Kei  東京歯科大学, 歯学部, 助教 (20733463)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords線維芽細胞 / コラーゲン / 歯周組織 / small GTPase / 細胞接着 / 細胞外マトリックス
Outline of Research at the Start

コラーゲンをはじめとした細胞外マトリックスのリモデリングは,様々な分子の相互作用により制御されている。線維芽細胞による細胞外マトリックスのリモデリングの不均衡は,臓器の線維化や組織の創傷治癒不全につながることが明らかとなっており,歯科においても歯肉増殖症,歯の骨性癒着をはじめとした種々の疾患の原因となっている。本研究では,cdc42の標的タンパク質であり細胞骨格の制御に関わることが知られているIQGAP1が,線維芽細胞の接着を介してコラーゲンのリモデリングにも影響を与えることを,分子生物学的に示すことを目的とした。

Outline of Final Research Achievements

An intracellular protein IQGAP1 is known to be involved in the regulation of the cytoskeleton. The purpose of this study was to investigate IQGAP1 affects collagen production and degradation (extracellular matrix remodeling) via fibroblast adhesion.
In fibroblast with knockdown of IQGAP1, the number of cell protrusions was reduced and migration ability was thought to be decreased. Furthermore, the phagocytosis and degradation of collagen were shown to be decreased in the knockdown cells. These results suggests that IQGAP1 affects extracellular matrix remodeling.

Academic Significance and Societal Importance of the Research Achievements

コラーゲンは体内で最も多いタンパク質であり、その生成と分解(細胞外マトリックスリモデリング)は、様々な分子の相互作用により制御されている。細胞外マトリックスリモデリングの不均衡は、歯科においても歯肉増殖症や歯の骨性癒着をはじめとした種々の疾患の原因となっている。本研究成果では、細胞骨格の制御に関わることが知られている細胞内タンパク質であるIQGAP1が、コラーゲンのリモデリングにも影響を与えることが示唆された。それにより、歯肉増殖症のような線維増生性病変における分子標的治療法・予防法の確立へと発展させることが可能であると考えられる。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 Other

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

  • [Int'l Joint Research] University of Toronto(カナダ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Toronto(カナダ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Role of the small GTPase activating protein IQGAP1 in collagen phagocytosis2021

    • Author(s)
      Nakajima Kei、Arora Pamela D.、Plaha Ajay、McCulloch Christopher A.
    • Journal Title

      Journal of Cellular Physiology

      Volume: 236 Issue: 2 Pages: 1270-1280

    • DOI

      10.1002/jcp.29933

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The effects of recombinant human basic fibroblast growth factor on nerve regeneration in a partial defect inferior alveolar nerve model in rabbits2021

    • Author(s)
      A.Nemoto, Y.Akashi, K.Nakajima, K.Kokubun, K.Sasaki, T.Inoue
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicie, and Pathology

      Volume: 33 Issue: 3 Pages: 348-353

    • DOI

      10.1016/j.ajoms.2020.12.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flightless anchors IQGAP1 and R-ras to mediate cell extension formation and matrix remodeling2020

    • Author(s)
      Arora P. D.、Nakajima K.、Nanda A.、Plaha A.、Wilde A.、Sacks D. B.、McCulloch C. A.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 31 Issue: 15 Pages: 1595-1610

    • DOI

      10.1091/mbc.e19-10-0554

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel model demonstrates the successful repair of alveolar cleft defects by tooth germ transplants2020

    • Author(s)
      Kei Nakajima, Yoshihiko Akashi, Masami Sumi, Takatoshi Chujo, Katsutoshi Kokubun, Kenichi Matsuzaka
    • Journal Title

      日本口腔検査学会雑誌

      Volume: 12 Pages: 46-52

    • NAID

      120006887039

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Role of IQGAP1- Flightless I interaction in collagen remodeling by fibroblast.2020

    • Author(s)
      Nakajima, K, Arora, PD, McCulloch, CA
    • Organizer
      62th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2023-01-30  

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