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Development of novel therapies for cardiovascular diseases by targeting immunosenescence

Research Project

Project/Area Number 18K15197
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49070:Immunology-related
Research InstitutionJuntendo University (2020)
Niigata University (2019)
Keio University (2018)

Principal Investigator

Shirakawa Kohsuke  順天堂大学, 医学(系)研究科(研究院), 学振特別研究員(PD) (30626388)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオステオポンチン / 心筋梗塞 / 心不全 / マクロファージ / 内臓脂肪 / 肥満 / 糖尿病 / 炎症
Outline of Final Research Achievements

We clarified that osteopontin (OPN) plays an essential role in accelerating both reparative fibrosis and clearance of dead cells (efferocytosis) during tissue repair after myocardial infarction (MI) and galectin-3hiCD206+ macrophages is the main source of OPN in post-MI heart. IL(Interleukin)-10-STAT3-galectin-3 axis is essential for Spp1 (encoding OPN) transcriptional activation in cardiac macrophages after MI. Furthermore, we also clarified that IL-10 and M-CSF act synergistically to activate STAT3 and ERK in cardiac macrophages, which in-turn upregulate the expression of galectin-3 and MerTK, leading to the functional maturation of OPN-producing macrophages.

Academic Significance and Societal Importance of the Research Achievements

虚血性心不全をはじめとした心不全の予後は進行癌と同様にきわめて予後不良である。
本研究では、心筋梗塞後創傷治癒過程におけるオステオポンチンの役割や産生細胞及びその分化機序を解明した。また、オステオポンチンをコントロールすることにより心筋梗塞後創傷治癒を促進し、心不全の病態を改善させる可能性を示した。

Report

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

    (5 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] MerTK Expression and ERK Activation Are Essential for the Functional Maturation of Osteopontin-Producing Reparative Macrophages After Myocardial Infarction2020

    • Author(s)
      Kohsuke Shirakawa, Jin Endo , Masaharu Kataoka, Yoshinori Katsumata, Atsushi Anzai, Hidenori Moriyama, Hiroki Kitakata, Takahiro Hiraide, Seien Ko, Shinichi Goto, Genki Ichihara, Keiichi Fukuda, Tohru Minamino, Motoaki Sano
    • Journal Title

      Journal of American Heart Association

      Volume: 9 Issue: 18

    • DOI

      10.1161/jaha.120.017071

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium-Glucose Co-Transporter 2 Inhibitors Correct Metabolic Maladaptation of Proximal Tubular Epithelial Cells in High-Glucose Conditions2020

    • Author(s)
      Shirakawa Kohsuke、Sano Motoaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 20 Pages: 7676-7676

    • DOI

      10.3390/ijms21207676

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of long term administration of tofogliflozin on chronic inflammation of visceral adipose tissue in mice with obesity induced by a high-fat diet2019

    • Author(s)
      Shirakawa Kohsuke、Yano Wataru、Inoue Keisuke、Katsumata Yoshinori、Endo Jin、Sano Motoaki
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0211387-e0211387

    • DOI

      10.1371/journal.pone.0211387

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Targeting Residual Inflammatory Risk: Promising Future for Cardiovascular Diseases ?2021

    • Author(s)
      Kohsuke Shirakawa
    • Organizer
      ISHR 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肥満関連疾患とオステオポンチン2019

    • Author(s)
      白川 公亮
    • Organizer
      CVMW 2019
    • Related Report
      2019 Research-status Report

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

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