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Mechanism and Biological Significance of Nucleolus-mediated Cell Fate Determination in Heart Failure

Research Project

Project/Area Number 16K19418
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionNara Medical University

Principal Investigator

Kumazawa Takuya  奈良県立医科大学, 医学部, 助教 (10745441)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心不全 / 細胞老化 / SASP / 核小体 / p53 / rRNA / rRNA / リボソーマルRNA
Outline of Final Research Achievements

Recently, the contribution of p53 to many undesirable aspects of age-associated diseases, such as cardiovascular disorders, has been recognized. p53 induced-cellular senescence have been implicated heart failure. Therefore, we examined the role of nucleolus mediated-cellular senescence in heart failure. Transverse aortic constriction (TAC), model of pressure overload-induced heart failure, increased transcription of rRNA, expression of SASP factors and SA-B-gal positive senescent cells in failing heart. Moreover coculture experiments demonstrated that senescent cardiac fibroblasts induced by increasing nucleolar RNA content promoted hypertrophy of cardiomyocytes. Hypertrophy of cardiomyocytes is associated with heart failure. These results implied that nucleolus mediated-cellular senescence contribute to exacerbation of heart failure. Thus, modulation of the nucleolus may represent a novel approach for treatment of heart disease.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2017 2016

All Presentation (10 results) (of which Int'l Joint Research: 5 results)

  • [Presentation] Nucleolar RNA content discriminates between apoptosis and cellular senescence and is involved in exacerbation of heart failure2017

    • Author(s)
      Takuya Kumazawa, Kazuho Nishimura, Keiji Kimura, and Yoshihiko Saito
    • Organizer
      2017 Keystone Symposia Noncoding RNAs: From Disease to Targeted Therapeutics
    • Place of Presentation
      Banff
    • Year and Date
      2017-02-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nucleolar RNA content discriminates between apoptosis and cellular senescence and is involved in exacerbation of heart failure2017

    • Author(s)
      Takuya Kumazawa, Kazuho Nishimura, Keiji Kimura, Yoshihiko Saito
    • Organizer
      2017 Keyston Symposia, Noncoding RNAs: From Disease to Targeted Therapeutics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanism and Biological Significance of Nucleolus-mediated Cell Fate Determination in Heart Failure2017

    • Author(s)
      熊澤拓也、西村和帆、木村圭志、斎藤能彦
    • Organizer
      第19回 日本RNA学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nucleolus-mediated Cellular Senescence is involved in Cardiac Hypertrophy2017

    • Author(s)
      Takuya Kumazawa, Kazuho Nishimura, Keiji Kimura, Yoshihiko Saito
    • Organizer
      AHA Scientific Sessions 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Novel Long Noncoding RNA Protects the Heart from Cardiorenal Syndrome Type42017

    • Author(s)
      熊澤拓也、斎藤能彦
    • Organizer
      第34回国際心臓研究学会日本部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A Novel Long Noncoding RNA LncX Suppresses the Progression of Cardio-renal Syndrome2017

    • Author(s)
      熊澤拓也、斎藤能彦
    • Organizer
      The 1st JCS Council Forum on Basic CardioVascular Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nucleolus-mediated cellular senescence signal contribute to cardiomyocyte hypertrophy2016

    • Author(s)
      Takuya Kumazawa, Kazuho Nishimura, Keiji Kimura, and Yoshihiko Saito
    • Organizer
      第33回 国際心臓研究会日本部会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-16
    • Related Report
      2016 Research-status Report
  • [Presentation] The nucleolus discriminates between apoptosis and cellular senescence and is involved in exacerbation of heart failure2016

    • Author(s)
      Takuya Kumazawa, Kazuho Nishimura, Keiji Kimura, and Yoshihiko Saito
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 核小体を介した細胞老化シグナルは心筋細胞肥大を引き起こす2016

    • Author(s)
      熊澤拓也、西村和帆、木村圭志、斎藤能彦
    • Organizer
      第7回Molecular Cardiovascular Conference II
    • Place of Presentation
      東京
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Fluctuations of Nucleolar RNA Content Discriminate between Apoptosis and Cellular Senescence2016

    • Author(s)
      3)Takuya Kumazawa, Kazuho Nishimura, Keiji Kimura, and Yoshihiko Saito
    • Organizer
      RNA2016 The 21st Annual Meetings of The RNA Society
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-06-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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