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Role of the redox-sensitive transcription factor Nrf2 in vascular neointimal hyperplasia

Research Project

Project/Area Number 24790785
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Circulatory organs internal medicine
Research InstitutionShowa University

Principal Investigator

ASHINO Takashi  昭和大学, 薬学部, 助教 (00338534)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords動脈硬化 / 酸化ストレス / 血管内膜肥厚 / 血管平滑筋細胞 / 細胞遊走 / 血小板由来増殖因子 / Nrf2 / 細胞増殖
Outline of Final Research Achievements

Reactive oxygen species (ROS) are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs), whereas excess ROS-induced oxidative stress contributes to the development of vascular diseases, such as atherosclerosis. Activation of Nrf2 system is pivotal in cellular defense against oxidative stress by transcriptional upregulation of antioxidant proteins. This study aimed to elucidate the role of Nrf2 in PDGF-mediated VSMC migration and neointimal hyperplasia. PDGF promoted nuclear translocation of Nrf2, followed by the induction of target genes. Nrf2 depletion enhanced PDGF-promoted ROS production and -enhanced VSMC migration. In vivo, Nrf2-deficient mice showed enhanced neointimal hyperplasia in a wire injury model. These findings suggest that the Nrf2 system plays an important role in PDGF-stimulated VSMC migration via regulating ROS elimination, which may contributes to neointimal formation after vascular injury.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (10 results) Remarks (2 results)

  • [Journal Article] Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver microsomes2014

    • Author(s)
      Ashino T, Hakukawa K, Itoh Y, Numazawa S
    • Journal Title

      J Toxicol Sci

      Volume: 39 Pages: 815-820

    • NAID

      130004704487

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible involvementof nuclear factor erythroid 2-related factor 2in the gene expression of Cyp2b10and Cyp2a52014

    • Author(s)
      Ashino T, Ohkubo-Morita H, Yamamoto M, Yoshida T, Numazawa S
    • Journal Title

      Redox Biology

      Volume: 10 Pages: 284-288

    • DOI

      10.1016/j.redox.2013.12.025

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IQGAP1 links PDGF receptor-β signal to focal adhesions involved in vascular smooth muscle cell migration: role in neointimal formation after vascular injury2013

    • Author(s)
      Kohno T, Urao N, Ashino T, Sudhahar V, Inomata H, Yamanaka-Tojo M, McKinney RD, Fukai T, Ushio-Fukai M
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 305 Issue: 6 Pages: C591-C600

    • DOI

      10.1152/ajpcell.00011.2013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Redox-sensitive transcription factor Nrf2 regulates vascular smooth muscle cell migration and neointimal hyperplasia2013

    • Author(s)
      Ashino T, Yamamoto M, Yoshida T, Numazawa S
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 33 Issue: 4 Pages: 760-768

    • DOI

      10.1161/atvbaha.112.300614

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel role of copper transport protein antioxidant-1 in neointimal formation after vascular injury.2013

    • Author(s)
      Kohno T
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: Apr; 33 (4) Issue: 4 Pages: 805-813

    • DOI

      10.1161/atvbaha.112.300862

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 危険ドラッグ含有合成カンナビノイドによる薬物代謝酵素シトクロムP450 阻害作用2015

    • Author(s)
      芦野 隆、伯川加菜絵、桜井彩華、伊藤有香、沼澤 聡
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      デザイン・クリエイティブセンター(神戸)
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Novel role of Kelch-like ECH-associated protein 1/NF-E2-related factor 2 system in vascular smooth muscle cell apoptosis following vascular injury2014

    • Author(s)
      Ashino T, Yamamoto M, Numazawa S
    • Organizer
      American Heart Association Scientific Sessions 2014
    • Place of Presentation
      McCormick Place(シカゴ)
    • Year and Date
      2014-11-15 – 2015-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 合成カンナビノイドによる薬物代謝酵素シトクロムP450 1A阻害作用2014

    • Author(s)
      芦野 隆、伊藤有香、伯川加菜絵、沼澤 聡
    • Organizer
      第41回日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(神戸)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] MCP-1によるマクロファージ遊走におけるNrf2の役割2014

    • Author(s)
      渡邊円香、芦野 隆、山本雅之、沼澤 聡
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Research-status Report
  • [Presentation] Regulatory mechanism of neointimal formation after vascular injury by redox-sensitive transcription factor Nrf22013

    • Author(s)
      Ashino T, Yamamoto M, Yoshida T, Numazawa S
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Coex(ソウル)
    • Related Report
      2013 Research-status Report
  • [Presentation] 転写因子Nrf2のROS-ERK経路を介した血管傷害後のリモデリング調節機構2013

    • Author(s)
      芦野 隆、山本雅之、吉田武美、沼澤 聡
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      幕張メッセ国際会議場(千葉)
    • Related Report
      2013 Research-status Report
  • [Presentation] The redox-sensitive transcription factor Nrf2 regulates reactive oxygen species-dependent vascular smooth muscle cell migration and neointimal hyperplasia

    • Author(s)
      Ashino T, Yamamoto M, Yoshida T, Numazawa S
    • Organizer
      The 10th Korea-Japan Joint Symposium on Vascular Biology
    • Place of Presentation
      あわぎんホール(徳島)
    • Related Report
      2012 Research-status Report
  • [Presentation] 血管内膜肥厚における酸化ストレス応答性転写因子Nrf2 の役割

    • Author(s)
      小柴 郁、芦野 隆、山本雅之、吉田武美、沼澤 聡
    • Organizer
      第56回日本薬学会関東支部大会
    • Place of Presentation
      昭和大学(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of the redox-sensitive transcription factor Nrf2 in vascular smooth muscle cell migration and vascular remodeling

    • Author(s)
      Ashino T, Yamamoto M, Yoshida T, Numazawa S
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2012 Research-status Report
  • [Presentation] 血管平滑筋細胞遊走および血管リモデリングにおけるレドックス感受性転写因子Nrf2の役割

    • Author(s)
      芦野 隆、山本雅之、吉田武美、沼澤 聡
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2012 Research-status Report
  • [Remarks] 昭和大学薬学部生体制御機能薬学講座毒物学部門ホームページ

    • URL

      http://www10.showa-u.ac.jp/~toxicol/index.htm

    • Related Report
      2014 Annual Research Report
  • [Remarks] 昭和大学薬学部生体制御機能薬学講座毒物学部門ホームページ

    • URL

      http://www10.showa-u.ac.jp/~toxicol/index.htm

    • Related Report
      2013 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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