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The role of arresten, a cleaved fragment of basement membrane type IV collagen alpha 1 chain, in the heart

Research Project

Project/Area Number 19K06428
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionKitasato University

Principal Investigator

Okada Muneyoshi  北里大学, 獣医学部, 准教授 (30453509)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsExtracellular matrix / Arresten / 心筋細胞 / 心線維芽細胞 / 心房筋 / 高血圧 / Angiotensin II / 心肥大 / 心筋梗塞
Outline of Research at the Start

IV型コラーゲンα1鎖C末端断片であるarrestenは心臓組織に豊富に存在するが、その生理学的意義は不明である。本研究ではarrestenが心臓構成細胞や摘出心臓標本に及ぼす影響を検討する。さらにarresten産生不全ラットを作出して表現型や心疾患の発症・進展との関連を検討することによりarrestenの病態生理学的役割を解明し、新たな心疾患治療戦略の標的因子としての応用可能性を探索する。

Outline of Final Research Achievements

Arresten is a bioactive fragment of type IV collagen α1 chain which constitutes the basement membrane around cardiomyocytes. However, its function in the heart has not been clarified. In this study, we used rodent cardiac cells, isolated cardiac tissue and hypertension model with cardiac hypertrophy to investigate the function of arresten in the heart. This study demonstrated that arresten has various physiological activities, such as promotion of migration in cardiac fibroblasts and cardiomyocyte hypertrophy induced by angiotensin II (AngII) in neonatal cardiomyocytes as well as changes in contraction and beating rate of atria. Furthermore, the expression of arresten tended to increase in hypertrophied left ventricular tissue from a rodent model of AngII-induced hypertension. This study suggests that arresten is an endogenous factor with various physiological activities in the heart.

Academic Significance and Societal Importance of the Research Achievements

本研究からarrestenが心臓において様々な生理活性を有する内因性因子であることが示唆された。また心肥大病態において発現が変動したことから、arrestenが心疾患の発症・進展において何らかの病態生理学的役割を担う可能性が考えられた。本研究成果を基に更に検討を行うことにより、arrestenを標的とした新規心疾患治療戦略の開発が進むことが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 Other

All Presentation (3 results) Remarks (2 results)

  • [Presentation] Expression of arresten and its role in the heart of rats with angiotensin II-induced hypertension2022

    • Author(s)
      岡田 宗善、栗原 秀弥、森 将就、大谷 紘資、山脇 英之
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] IV型コラーゲンα1鎖分解断片arrestenがラット新生仔心筋細胞の酸化ストレス誘導性細胞死およびangiotensin II誘導性肥大に及ぼす影響2021

    • Author(s)
      栗原 秀弥、岡田 宗善、大谷 紘資、山脇 英之
    • Organizer
      第34回北里大学バイオサイエンスフォーラム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Arresten, a cleaved fragment of type IV collagen α1 chain, regulates functions of cardiac fibroblasts and left atria2021

    • Author(s)
      杉山 彰、田嶋 志帆、山本 理幾、大谷 紘資、岡田 宗善、山脇 英之
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Remarks] 北里大学獣医薬理学研究室ホームページ

    • URL

      http://www.vmas.kitasato-u.ac.jp/pharmacology/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 北里大学獣医薬理学研究室

    • URL

      http://www2.vmas.kitasato-u.ac.jp/pharmacology/

    • Related Report
      2020 Research-status Report 2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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