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The treatments of proliferative vitreoretinopathy by inhibition of TGF-b signaling

Research Project

Project/Area Number 20592050
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionOita University

Principal Investigator

KIMOTO Kenichi  Oita University, 医学部, 講師 (50315339)

Co-Investigator(Kenkyū-buntansha) YOSHIOKA Hidekatsu  大分大学, 医学部, 教授 (00222430)
MATSUO Noritaka  大分大学, 医学部, 准教授 (10284788)
篠田 啓  大分大学, 医学部, 准教授 (60245561)
中塚 和夫  大分大学, 医学部, 教授 (20112378)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords眼細胞生物学 / 網膜色素上皮 / 増殖性硝子体網膜症 / コラーゲン / シグナル伝達 / TGF-β / 分子標的治療 / 網膜色素上皮細胞 / 細胞外マトリックス / PKC-δ / PI3K/Akt / Smad / PI3K
Research Abstract

Transforming growth factor (TGF)-β is a key mediator of proliferative vitreoretinopathy, but the cellular mechanisms by which TGF-β induces extracellular matrix protein (ECM) synthesis are not fully understood. This study examined whether the PI3K/Akt pathway is involved in TGF-β2-induced collagen expression in human retinal pigment epithelial cells. The biochemical blockade of PI3K/Akt activation inhibited TGF-β2-induced type I collagen mRNA expression and type I collagen synthesis. The blockade of PI3K/Akt pathway inhibited the increase in COL1A2 promoter activities when induced by TGF-β2 and reduced TGF-β2 induction of Smad-mut/Luc promoter activity and CAGA12-Luc activity. Moreover, wortmannin increased the TGF-β2-induced Smad7 mRNA expression levels. The PI3K/Akt pathway plays a role in relaying the TGF-β2 signal to induce type I collagen synthesis in the retinal pigment epithelium through Smad-dependent and Smad-independent pathway.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (8 results)

All 2010 2009 2008 Other

All Journal Article (2 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] 糖尿病合併症の成因と対策糖尿病網膜症2009

    • Author(s)
      木許賢一, 中塚和夫
    • Journal Title

      臨床と研究 86

      Pages: 45-49

    • Related Report
      2008 Annual Research Report
  • [Journal Article] PI3K/Akt mediates the expression of type I collagen induced by TGF-b2 in human retinal pigment epithelium

    • Author(s)
      Yokoyama K, Kimoto K, Itoh Y, Nakatsuka K, Matsuo N, Yoshioka H, Kubota T.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol in press.

    • Related Report
      2010 Final Research Report
  • [Presentation] PI3K/Akt mediates the expression of type I collagen induced by TGF-b2 in human retinal pigment epithelium2010

    • Author(s)
      Yokoyama K, Kimoto K, Kubota T
    • Organizer
      World Ophthalmology Congress 2010
    • Place of Presentation
      ベルリン
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] PI3K/Akt mediates the expression of type I collagen induced by TGF-b2 in human retinal epithelial cells2009

    • Author(s)
      Yokoyama K, Kimoto K, et al.
    • Organizer
      The 2nd Joint Meeting of Japan-China-Korea Ophthalmologists
    • Place of Presentation
      Fukuoka
    • Year and Date
      2009-11-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 網膜色素上皮細胞のコラーゲン発現におけるPl3K/Akt経路の関与2008

    • Author(s)
      横山勝彦、木許賢一, ほか
    • Organizer
      第112回日本眼科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 網膜色素上皮細胞のコラーゲン発現におけるP13K/Akt経路の関与2008

    • Author(s)
      横山勝彦, 木許賢一, 他
    • Organizer
      第112回日本眼科学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-04-17
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks] 大分大学眼科ホームページ

    • URL

      http://www.med.oita-u.ac.jp/ganka/

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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