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Pathological functions of cardiac fibroblasts in pediatric cardiomyopathy

Research Project

Project/Area Number 18K07789
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionOsaka University

Principal Investigator

ISHII RYO  大阪大学, 医学系研究科, 助教 (90794008)

Co-Investigator(Kenkyū-buntansha) 石田 秀和  大阪大学, 医学系研究科, 助教 (50467552)
小垣 滋豊  大阪大学, 医学系研究科, 招へい教員 (00311754)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords心筋症 / 心筋線維芽細胞 / 心筋細胞 / 遺伝子発現解析 / 心臓移植 / 拡張型心筋症 / RNA-seq / 拘束型心筋症
Outline of Final Research Achievements

The precise molecular mechanisms of idiopathic cardiomyopathy is still unknown. We performed whole exome analysis for Japanese pediatric cardiomyopathy patients and identified lots of gene mutations which cause cardiomyopathy in children. We cultured cardiac fibroblasts obtained from the various cardiomyopathy patients while the heart transplantation or ventricular assist device implantation. The diseased cardiac fibroblasts show significant different gene expression patterns as compared to the healthy cardiac fibroblasts. When we co-cultured the healthy cardiomyocytes with diseased cardiac fibroblasts, the cardiomyocytes showed weaken contraction and dilatation ability. We established induced pluripotent stem cell lines from the patients with idiopathic cardiomyopathy in children.

Academic Significance and Societal Importance of the Research Achievements

今回の私達の研究により、これまで心筋細胞にのみ原因があると考えられてきた特発性心筋症の病態において、心筋線維芽細胞が重要な役割を果たしていることが明らかとなった。心筋症の患者から得られた心筋線維芽細胞が、健常な心筋細胞の収縮能や拡張能に悪影響を与えているということは大きな発見である。今後、心筋細胞だけでなく心筋線維芽細胞もターゲットとした新しい治療法の開発につながる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2021 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Cardiac Fibroblasts Play Pathogenic Roles in Idiopathic Restrictive Cardiomyopathy2021

    • Author(s)
      Tsuru Hirofumi、Ishida Hidekazu、Narita Jun、Ishii Ryo、Suginobe Hidehiro、Ishii Yoichiro、Wang Renjie、Kogaki Shigetoyo、Taira Masaki、Ueno Takayoshi、Miyashita Yohei、Kioka Hidetaka、Asano Yoshihiro、Sawa Yoshiki、Ozono Keiichi
    • Journal Title

      Circulation Journal

      Volume: 85 Issue: 5 Pages: 677-686

    • DOI

      10.1253/circj.CJ-20-1008

    • NAID

      130008028981

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2021-04-23
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 小児心筋症における心筋線維芽細胞の生理機能ならびに病態関与の解析2020

    • Author(s)
      水流宏文, 石田秀和, 杉辺英世, 桂木慎一, 石井 良, 成田 淳, 上野高義, 小垣滋豊, 澤 芳樹, 大薗恵一
    • Organizer
      第56回 日本小児循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 心筋線維芽細胞に着目した小児心筋症の病態解明と治療応用2019

    • Author(s)
      水流宏文、石井良ら
    • Organizer
      第55回 日本小児循環器学会総会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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