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Epigenetic regulation during maturation of endothelial cell

Research Project

Project/Area Number 18K14914
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

TANAKA TORU  国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (50806065)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords血管内皮細胞 / 転写制御 / エピジェネティクス / ヒストン修飾 / 細胞分化 / HDAC / 分化
Outline of Final Research Achievements

Endothelial cells (ECs) mature into arterial and venous ECs, and then change gene expression. The differences in gene expression are important in vasculogenesis. However, the mechanisms of arterial/venous EC specific gene expression are poorly understood. In this study, I focused on epigenetic modification and investigated the molecular mechanism that produces the specificity of arterial and venous ECs. I found that the inhibitors of a particular histone modifier suppressed the arterial maturation of ECs and increased the expression of vein-specific genes. These data suggest that the histone modifier function is involved in the arterial maturation.

Academic Significance and Societal Importance of the Research Achievements

動脈・静脈内皮細胞がそれぞれの特異性を持つことは正常な血管形成に不可欠である。内皮細胞の成熟においてエピゲノムがどのように規定され遺伝子発現を制御するかを理解することは血管形成の分子機構を知る重要な手がかりとなり、効率的な血管内皮細胞への分化誘導法の開発、再生医療への応用に繋がる。また、死因の上位を占める疾患(癌、心疾患、脳血管障害)には血管形成が関連しており、将来的にエピジェネティック修飾因子を標的とした治療薬が血管関連疾患の新規治療法への応用に役立つことが期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Significance of Hey transcription factors in endothelial cell differentiation and embryonic vascular development2019

    • Author(s)
      Toru TANAKA, Norika LIU, Shoko TAMURA, Daiki SEYA, Yusuke WATANABE, Osamu NAKAGAWA
    • Organizer
      Vascular Biology 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transcriptional regulation and physiological significance of ALK1 target genes in endothelial cells2018

    • Author(s)
      Norika LIU, Yukihiro HARADA, Toru TANAKA, Teruhisa KAWAMURA, Yoshihiko SAITO, Osamu NAKAGAWA
    • Organizer
      日本血管生物医学会 第16回Korea-Japan Joint Symposium
    • Related Report
      2018 Research-status Report
  • [Presentation] 血管形成期における新規ALK1ターゲット遺伝子SGK1の血管内皮細胞特異的発現機構2018

    • Author(s)
      原田恭弘、田中亨、渡邉裕介、荒井勇二、磯本祥恵、中野厚史、川村晃久、中川修
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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