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Metabolic Plasticity in Cell State Homeostasis and Differentiation of Cultured Human Corneal Endothelial Cells as A New Target for Drug Development

Research Project

Project/Area Number 26670759
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SOTOZONO CHIE  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30216585)

Co-Investigator(Kenkyū-buntansha) 羽室 淳爾  京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (80536095)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords角膜内皮細胞 / エネルギー代謝応答 / 解糖系 / ミトコンドリア / 代謝リモデリング / miRNA / 細胞相転移 / ヒト角膜内皮細胞 / 相転移 / CD44 / SASP / エネルギー代謝経路 / 細胞亜集団 / 培養ヒト角膜内皮細胞 / EMT / メタボローム解析 / 解糖系エネルギー代謝
Outline of Final Research Achievements

In this study, we found the way, using the culture supernatants, to discrimiーnate SPs in cHCECs in terms of their secretory metabolites, and found that the CST SPs exhibited the disposition to the anaerobic glycolysis instead of mitoc-hondria-dependent OXPHOS. The study on the secretory metabolites assigned the cHCEC SPs distinct in the expression levels of surface CD44 antigen. Transition from oxidative metabolism into glycolysis is a prerequisite for reprogramming to the pluripotent state. Conversely, redirection of pluripotency into defined lineages requires mito- chondrial biogenesis and maturation of efficient oxidative energy generati- on.The reduction of glycolysis might be triggered by downregulation of the cMyc pathway.Our novel findings provide evidence of a possible link between metabo-lic regulation in the corneal endothelium and the development of more effective targeted therapies to treat patients with bullous keratopathy, including FECD.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2016 2015

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human Corneal Endothelial Cells.2016

    • Author(s)
      Hamuro J, Toda M, Asada K, Hiraga A, Schlötzer-Schrehardt U, Montoya M,
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 57 Issue: 11 Pages: 4749-4761

    • DOI

      10.1167/iovs.16-19770

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 8.Metabolic Plasticity in Cell State Homeostasis and Differentiation of Cultured Human Corneal Endothelial Cells.2016

    • Author(s)
      Hamuro J, Ueno M, Asada K, Toda M, Montoya M, Sotozono C, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 57 Issue: 10 Pages: 4452-4463

    • DOI

      10.1167/iovs.16-19807

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Concomitant Evaluation of a Panel of Exosome Proteins and MiRs for Qualification of Cultured Human Corneal Endothelial Cells2016

    • Author(s)
      Morio Ueno, Kazuko Asada, Munetoyo Toda, Kazue Nagata, Chie Sotozono, Nobuyoshi Kosaka, Takahiro Ochiya, Shigeru Kinoshita, Junji Hamuro
    • Organizer
      IISEV2016
    • Place of Presentation
      Rotterdam, Netherland
    • Year and Date
      2016-05-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of dysregulated expression of miRs in pathogenesis of BK and FECD2016

    • Author(s)
      Kazuko Asada, Morio Ueno, Munetoyo Toda, Asako Hiraga, Monty Montoya, Chie Sotozono, Shigeru Kinoshita
    • Organizer
      87th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      シアトル市、USA
    • Year and Date
      2016-04-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 角膜内皮細胞機能不全におけるepigeneticな細胞機能制御2016

    • Author(s)
      浅田 和子、上野 盛夫、戸田宗豊、平賀朝子、落谷孝広、外園千恵、木下茂、羽室淳爾
    • Organizer
      日本眼科学会総会
    • Place of Presentation
      仙台市
    • Year and Date
      2016-04-07
    • Related Report
      2015 Research-status Report
  • [Presentation] Regulation of mitochondrial respiration under cell culture stress in human corneal endothelial cells2016

    • Author(s)
      Kinoshita S, Ueno M, Asada K, Toda M, Nagata K, Sotozono C, Kosaka N, Ochiya T, Hamuro J
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic plasticity in the cell-state homeostasis and differentiation of cultured human corneal endothelial cells2016

    • Author(s)
      Hamuro J, Ueno M, Asada K, Toda M, Montoya M, Sotozono C, Kinoshita S.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of cytokines in serum and aqueous humor in patients with bullous keratopathy2015

    • Author(s)
      Morio Ueno, Munetoyo Toda, Asako HIraga, Naomi Tobita, Hiroko Nakagawa, Chie Sotozono, Noriko Koizumi, Naoki Okumura, Kazuko Asada, Junji Hamuro, and Shigeru Kinoshita
    • Organizer
      87th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      Denver, Colorado, USA
    • Year and Date
      2015-05-06
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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