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Identification and characterization of novel myeloid cells that infiltrate into post-infarct myocardium

Research Project

Project/Area Number 20K21575
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionOsaka University

Principal Investigator

Fujio Yasushi  大阪大学, 薬学研究科, 教授 (20359839)

Co-Investigator(Kenkyū-buntansha) 尾花 理徳  大阪大学, 薬学研究科, 准教授 (50745883)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords心筋炎症 / 心筋梗塞 / 心筋リモデリング
Outline of Research at the Start

社会の高齢化に伴い慢性心不全患者が増加している。中でも、心筋梗塞後に発症する心不全は、薬物治療に抵抗性を示すため予後が悪いということが知られている。近年、心筋梗塞後に心不全が発症する過程に炎症反応が関与していることが知られるようになってきたが、詳細は依然不明である。本研究では、我々が新たに見出した骨髄由来炎症関連細胞に着目し、その機能を解明する。本研究の成果から、当該細胞の機能を制御することによる新規心不全治療法が開発される可能性が期待される。

Outline of Final Research Achievements

Myocardial infarction results in the infiltration of myeloid cells into the heart, which modulates post-infarct inflammation of myocardium. So far, neutrophils and monocytes / macrophages have been believed to play important roles in this process; however, recently, accumulating evidence has demonstrated that myeloid cells are composed of wider ranges of cell populations than expected.
In this project, we performed the single cell RNA seq analysis using myeloid cells that infiltrated into post-infarct myocardium and identified a cell cluster that is different from the cluster of neutrophils or from that of monocytes / macrophages. Next, we prepared this cell population to examine gene expression profile by RNA seq assay and found that this cluster is a novel cell population.

Academic Significance and Societal Importance of the Research Achievements

社会の高齢化に伴い循環器疾患が増加し、その結果、心不全が急増している。心不全の中でも心筋梗塞後に発症する心不全は、薬物治療に抵抗性を示すため、その発症予防は喫緊の課題である。梗塞後心不全の発症には、心筋組織に浸潤する骨髄由来細胞が重要な役割を演じていることが知られているが、それらの細胞の多様性ゆえに、詳細なメカニズムの理解には至っていない。本研究では、従来報告されていなかった新たな細胞集団が梗塞後心筋組織に浸潤することを見出し、その機能解明を行っている。この細胞集団の機能制御を戦略とする、新規心不全治療法の開発につながることが期待される。

Report

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

    (17 results)

All 2022 2021 2020 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Yes‐associated protein activation potentiates glycogen synthase kinase‐3 inhibitor‐induced proliferation of neonatal cardiomyocytes and iPS cell‐derived cardiomyocytes2022

    • Author(s)
      Kametani Y, Tanaka S, Wada Y, Suzuki S, Umeda A, Nishinaka K, Okada Y, Maeda M, Miyagawa S, Sawa Y, Obana M, Fujio Y.
    • Journal Title

      Journal of Cellular Physiology

      Volume: 237 Issue: 5 Pages: 2539-2549

    • DOI

      10.1002/jcp.30724

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular Endothelial Growth Factor Receptor Inhibitors Impair Left Ventricular Diastolic Functions2021

    • Author(s)
      Haruka Yokoyama, Wataru Shioyama, Takuya Shintani, Shinichiro Maeda, Sachiko Hirobe, Makiko Maeda, Yasushi Sakata, Yasushi Fujio
    • Journal Title

      International Heart Journal

      Volume: 62 Issue: 6 Pages: 1297-1304

    • DOI

      10.1536/ihj.21-307

    • NAID

      130008122384

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2021-11-29
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PKNOX2 regulates myofibroblast functions and tubular cell survival during kidney fibrosis2021

    • Author(s)
      Miyake Y, Obana M, Nakae T, Yamamoto A, Tanaka S, Maeda M, Okada Y, Fujio Y.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 571 Pages: 88-95

    • DOI

      10.1016/j.bbrc.2021.07.067

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maresin-1 induces cardiomyocyte hypertrophy through IGF-1 paracrine pathway2021

    • Author(s)
      Wahyuni T, Kobayashi A, Tanaka S, Miyake Y, Yamamoto A, Bahtiar A, Mori S, Kametani Y, Tomimatsu M, Matsumoto K, Maeda M, Obana M, Fujio Y.
    • Journal Title

      American Journal of Physiology-Cell Physiology

      Volume: 321 Issue: 1 Pages: C82-C93

    • DOI

      10.1152/ajpcell.00568.2020

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Title: Gene Transfer by Pyro-Drive Jet Injector is a Novel Therapeutic Approach for Muscle Diseases2021

    • Author(s)
      Nakae Takafumi、Obana Masanori、Maeda Takahiro、Ikeda Akari、Miyazaki Hiroshi、Tanaka Shota、Maeda Makiko、Yamashita Kunihiko、Terai Kazuhiro、Obika Satoshi、Fujio Yasushi
    • Journal Title

      Gene

      Volume: in press Pages: 145664-145664

    • DOI

      10.1016/j.gene.2021.145664

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis2020

    • Author(s)
      Yamamoto Ayaha、Morioki Hitomi、Nakae Takafumi、Miyake Yoshiaki、Harada Takeo、Noda Shunsuke、Mitsuoka Sayuri、Matsumoto Kotaro、Tomimatsu Masashi、Kanemoto Soshi、Tanaka Shota、Maeda Makiko、Conway Simon J.、Imaizumi Kazunori、Fujio Yasushi、Obana Masanori
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 2

    • DOI

      10.1096/fj.202001820r

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adenovirus Vector?Induced IL-6 Promotes Leaky Adenoviral Gene Expression, Leading to Acute Hepatotoxicity2020

    • Author(s)
      Shimizu Kahori、Sakurai Fuminori、Iizuka Shunsuke、Ono Ryosuke、Tsukamoto Tomohito、Nishimae Fumitaka、Nakamura Shin-ichiro、Nishinaka Toru、Terada Tomoyuki、Fujio Yasushi、Mizuguchi Hiroyuki
    • Journal Title

      The Journal of Immunology

      Volume: 206 Issue: 2 Pages: 410-421

    • DOI

      10.4049/jimmunol.2000830

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Increased Old Astrocyte Specifically Induced Scbstance (OASIS) in podocytes leads to the progression of nephrotic syndrome2021

    • Author(s)
      Miyake Y, Obana M, Yamamoto A, Noda S, Tanaka K, Tanaka S, Maeda M, Asanuma K, Fujio Y.
    • Organizer
      American Society of Nephrology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TGFβ3は梗塞後心筋リモデリングを増悪させる2021

    • Author(s)
      冨松 聖史、横田 洸成、小南 春祐、田中 翔大、前田 真貴子、岡田 欣晃、尾花 理徳、藤尾 慈
    • Organizer
      第95回日本薬理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 培養心筋細胞における内因性YAP活性は、GSK3阻害剤による増殖誘導効果を増強する2021

    • Author(s)
      亀谷祐介、田中翔大、鈴木翔大、梅田綾香、前田真貴子、岡田欣晃、尾花理徳、藤尾慈
    • Organizer
      第31回日本循環薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞周期感受性タンパクFUCCIを用いた新規心筋増殖関連因子の網羅的探索2021

    • Author(s)
      和田 祐理子、亀谷 祐介、鈴木 翔大、梅田 綾香、西中 康介、田中 翔大、前田 真貴子、岡田 欣晃、尾花 理徳、藤尾 慈
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Activation of YAP is essential for the myocardial recovery from myocarditis2021

    • Author(s)
      福山尚希、亀谷祐介、和田祐理子、鈴木翔大、梅田綾香、前田真貴子、田中翔大、尾花理徳、藤尾 慈
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Cardioprotective roles of novel cell death inhibitor, defender against cell death 1 (Dad1)2021

    • Author(s)
      森 翔太、田中翔大、前田真貴子、尾花理徳、藤尾 慈
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] CXCL10 is an anti-angiogenic factor downstream of p53 in cardiomyocytes2021

    • Author(s)
      五十嵐竜太、冨松聖史、前田真貴子、田中翔大、尾花理徳、藤尾 慈
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Molecular mechanisms of myocardial reverse remodeling after myocarditis2020

    • Author(s)
      Yasushi Fujio
    • Organizer
      Basic Cardiovascular Science 2020 Scientific Sessions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 大阪大学大学院薬学研究科 臨床薬効解析学分野

    • URL

      https://www.phs.osaka-u.ac.jp/homepage/b014/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 大阪大学大学院薬学研究科・薬学部

    • URL

      http://www.phs.osaka-u.ac.jp/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2025-01-30  

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