• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification of novel therapeutic targets for cardiac fibrosis

Research Project

Project/Area Number 18K06898
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48030:Pharmacology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Iwata Kazumi  京都府立医科大学, 医学(系)研究科(研究院), 講師 (60305571)

Co-Investigator(Kenkyū-buntansha) 松本 みさき  京都府立医科大学, 医学(系)研究科(研究院), 助教 (80533926)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心線維化 / 活性酸素種 / NADPHオキシダーゼ / 心不全
Outline of Final Research Achievements

We previously presented that doxorubicin-induced cardiac fibrosis was suppressed in the mice which deficient of NOX1/NADPH oxidase. We studied the role of NOX1 in the cardiac fibrosis using H9c2 cells, a rat cardiomyoblast cell line, and primary cultures of cardiac fibroblasts isolated from adult male mice. Increased proliferation of cardiac fibroblasts induced by transforming growth factor-β (10 ng/ml) or fetal bovine serum (1%) was significantly suppressed when cardiac fibroblasts were exposed to homogenates from Nox1-diurupted H9c2, but not from wild-type cells. In Nox1-disrupted H9c2 cells, expression of Collagen4a1 (Col4a), Osteoglycin (Ogn), and Podocan (Podn) were up-regulated. When the homogenates from Col4a -, Ogn -, or Podn -disrupted H9c2 were exposed to cardiac fibroblasts, suppressed proliferation was significantly restored. These findings suggest that NOX1 promotes cardiac fibrosis via down-regulation of fibrosis inhibitory factors in cardiomyocytes.

Academic Significance and Societal Importance of the Research Achievements

我が国では左室駆出率の保持された心不全 (Heart Failure with Preserved Ejection Fraction: HFpEF) が心不全患者の50%以上を占めるものの、予後を改善する治療法がない現状である。HFpEFの主因は心筋細胞の肥大と線維化による拡張不全であることから、本研究ではHFpEFの新しい治療法の開発に向け、心臓の線維化を抑制する新しい分子の同定とその作用機構について検討を行った。

Report

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

    (6 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] NOX1/NADPH oxidase in bone marrow-derived cells modulates intestinal barrier function2020

    • Author(s)
      Liu J, Iwata K, Zhu K, Matsumoto M, Asaoka N, Zhang X, Ibi M, Katsuyama M, Tsutsui M, Kato S, and Yabe-Nishimura C
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 147 Pages: 90-101

    • DOI

      10.1016/j.freeradbiomed.2019.12.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NOX1/ NADPH oxidase regulates the expression of multidrug resistance‐associated protein 1 and maintains intracellular glutathione levels2019

    • Author(s)
      Wen Xiaopeng、Iwata Kazumi、Ikuta Keiko、Zhang Xueqing、Zhu Kai、Ibi Masakazu、Matsumoto Misaki、Asaoka Nozomi、Liu Junjie、Katsuyama Masato、Yabe‐Nishimura Chihiro
    • Journal Title

      The FEBS Journal

      Volume: 286 Issue: 4 Pages: 678-687

    • DOI

      10.1111/febs.14753

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] NOX1/NADPHオキシダーゼによる心線維化抑制因子の発現調節2021

    • Author(s)
      岩田和実,矢部千尋
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] メタボリックシンドロームの形成に関わる菌血症と腸管バリア機能障害-活性酸素生成酵素NOX1/NADPHオキシダーゼの役割2020

    • Author(s)
      岩田和実,劉俊傑,矢部千尋
    • Organizer
      第35回日本糖尿病合併症学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Up-regulation of NOX1/NADPH oxidase following myocardial cell injury plays a critical role in the development of cardiac fibrosis2018

    • Author(s)
      KazumiIwata,KuniharuMatsunoandChihiroYabe-Nishimura
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Up-regulation of NOX1/NADPH oxidase following myocardial cell injury plays a critical role in the development of cardiac fibrosis2018

    • Author(s)
      Kazumi Iwata and Chihiro Yabe-Nishimura
    • Organizer
      NOX Family NADPH OxidasesGordon Research Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi