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Regulation mechanism of corneal stem cell differentiation and proliferation by oxygen concentration

Research Project

Project/Area Number 21592264
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SHIMMURA Shigeto  慶應義塾大学, 医学部 (00235780)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHypoxia inducible factor(HIF) / 幹細胞 / 低酸素培養 / 角膜上皮細胞 / Hypoxia inducible factor (HIF) / 細胞周期 / 増殖 / Hyoxia inducible factor (HIF) / 分化
Research Abstract

Hypoxia promotes proliferation of corneal epithelial stem cells isolated from human limbus. Hypoxia is detected by hypoxia inducible factor(HIF). Three HIF-a isoforms are known ; HIF-1a, HIF-2a, and HIF-3a. In this study, expression and function of HIF-a in human corneal epithelial cells were investigated. RT-PCR analysis and Western blot analysis confirmed both primary cultured human limbal epithelial cells(LEC) and corneal epithelial cell line HCE-T expressed HIF-1a, HIF-2a, and HIF-3a. Inhibition of HIF-1a by specific siRNA did not influence on the proliferation of LEC and HCET, HIF-2a siRNA inhibited. Over expressions of HIF-1a or HIF-2a did not effect on proliferation. These data suggest the relationship between HIF-2a and proliferation of corneal epithelial stem cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (16 results)

All 2011 2010 2009

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (10 results)

  • [Journal Article] Fate of corneal epithelial cells separated from limbus in vivo2011

    • Author(s)
      Kawakita T, Higa K, Shimmura S, Tomita M, Tsubota K, Shimazaki J
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 52 Issue: 11 Pages: 8132-8137

    • DOI

      10.1167/iovs.11-7984

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clusterin promotes corneal epithelial cell growth through upregulation of hepatocyte growth factor by mesenchymal cells in vitro2011

    • Author(s)
      Okada N, Kawakita T, Mishima K, Saito I, Miyashita H, Yoshida S, Shimmura S, Tsubota K
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 52(6) Issue: 6 Pages: 7888-7893

    • DOI

      10.1167/iovs.10-6348

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-cadherin in the maintenance of human corneal limbal epithelial progenitor cells in vitro2009

    • Author(s)
      Higa, K.Shimmura, S.(corresponding)Miyashita, H.Kato, N.Ogawa, Y.Kawakita, T.Shimazaki, J.Tsubota, K.
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 4640-4645

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term culture and growth kinetics of murine corneal epithelial cells expanded from single corneas2009

    • Author(s)
      Ma, X.Shimmura, S.(corresponding)Miyashita, H.Yoshida, S.Kubota, M.Kawakita, T.Tsubota, K.
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 2716-2721

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease2009

    • Author(s)
      Ogawa, Y.Shimmura, S.(corresponding)Kawakita, T.Yoshida, S.Kawakami, Y.Tsubota, K.
    • Journal Title

      Am J Pathol 175

      Pages: 2372-2381

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The use of human mesenchymal stem cell-derived feeder cells for the cultivation of transplantable epithelial sheets2009

    • Author(s)
      Omoto, M.Miyashita, H.Shimmura, S.(corresponding)Higa, K.Kawakita, T.Yoshida, S.McGrogan, M.Shimazaki, J.Tsubota, K.
    • Journal Title

      Invest Ophthalmol Vis Sci 50

      Pages: 2109-2115

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Inhibition of hypoxia inducible factor 2 alpha in human corneal epithelial cells delays cell cycle at G2 phase even under normoxia2011

    • Author(s)
      Hideyuki Miyashita, Shigeto Shimmura, Miyuki Kubota, Kazuo Tsubota
    • Organizer
      The 2012 ARVO (Association for Research in Vision and Ophthalmology) annual meeting
    • Place of Presentation
      Fort Lauderdale, Florida, USA
    • Year and Date
      2011-05-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Inhibition of hypoxia inducible factor 2 alpha in human corneal epithelial cells delays cell cycle at G2 phase even under normoxia2011

    • Author(s)
      Miyashita H, Shimmura S, Kubota M, Tsubota K
    • Organizer
      The Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] 角膜上皮前駆細胞における、HIF2Aによる細胞周期G2進行制御2011

    • Author(s)
      宮下英之、久保田みゆき、吉田悟、関口友美、坪田一男、榛村重人
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒト角膜上皮細胞における、HIF-2Aによる細胞周期制御2011

    • Author(s)
      宮下英之、久保田みゆき、吉田悟、関口友美、坪田一男、榛村重人
    • Organizer
      第35回角膜カンファランス
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] 角膜上皮細胞内 Clusterin の細胞増殖および酸化ストレスへの役割2010

    • Author(s)
      岡田直子, 榛村重人, 川北哲也, 川島素子, 美島健二, 齋藤一郎, 坪田一男
    • Organizer
      第34回角膜カンファランス
    • Place of Presentation
      仙台
    • Year and Date
      2010-02-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] フィーダーが無血清培地中のヒト角膜輪部上皮の細胞寿命に与える影響2010

    • Author(s)
      宮下英之, 榛村重人, 坪田一男
    • Organizer
      第34回角膜カンファランス
    • Place of Presentation
      仙台
    • Year and Date
      2010-02-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウスiPS細胞由来の上皮細胞を用いた重層化上皮シート作成2010

    • Author(s)
      吉田悟, 榛村重人, 坪田一男
    • Organizer
      第34回角膜カンファランス
    • Place of Presentation
      仙台
    • Year and Date
      2010-02-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 角膜再生医療2009

    • Author(s)
      榛村重人
    • Organizer
      第25回日本DDS学会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス涙腺慢性移植片対宿主病モデルにおける病的線維化の発症と進展機序の解析2009

    • Author(s)
      小川葉子, 榛村重人, 稲葉隆明, 河上裕, 岡野栄之, 坪田一男
    • Organizer
      第113回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] SOD1による角膜血管新生の抑制2009

    • Author(s)
      久保田みゆき, 栗原俊英, 久保田俊介, 石田晋, 坪田一男, 榛村重人
    • Organizer
      第113回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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