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Elucidation of the role of epigenetic regulation by NRSF complex in maintaining cardiac integrity

Research Project

Project/Area Number 25860596
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionKyoto University

Principal Investigator

KUWABARA Yoshihiro  京都大学, 医学(系)研究科(研究院), 研究員 (40647400)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords転写因子 / NRSF / 心不全 / エピゲノム / 循環器 / ノックアウトマウス
Outline of Final Research Achievements

In this study, I succeeded to generate cardiac-specific NRSF conditional knockout mice (NRSF ccKO) and found that these mice show cardiac dysfunction, malignant arrhythmias and sudden cardiac death, implying that NRSF plays an essential role in maintaining normal cardiac function. To address the underlying mechanisms, I crossed these mice with HDAC1/2 cardiac-specific double heterozygote knockout mice and analyzed NRSF/HDAC1/2 cardiac-specific triple heterozygote knockout mice. I also found that GNAO1 gene expression is increased in NRSF ccKO. To examine the contribution of G alpha O to cardiac dysfunction seen in NRSF ccKO, I treated these mice with PTX and found that PTX improved cardiac function and the survival curve in NRSF ccKO. Currently I am further analyzing the role of G alpha O in the phenotype of NRSF ccKO.

Report

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

    (11 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (3 results) Remarks (2 results)

  • [Journal Article] Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.2015

    • Author(s)
      Oshita K, Itoh M, Hirashima S, Kuwabara Y, Ishihara K, Kuwahara K, Nakao K, Kimura T, Nakamura K, Ushijima K, Takano M.
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 80 Pages: 81-89

    • DOI

      10.1016/j.yjmcc.2014.12.019

    • NAID

      120007100131

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.2014

    • Author(s)
      Yamada Y, Kinoshita H, Kuwahara K, Nakagawa Y, Kuwabara Y, Minami T, Yamada C, Shibata J, Nakao K, Cho K, Arai Y, Yasuno S, Nishikimi T, Ueshima K, Kamakura S, Nishida M, Kiyonaka S, Mori Y, Kimura T, Kangawa K, Nakao K.
    • Journal Title

      Cardiovasc Research

      Volume: 104 Issue: 1 Pages: 183-193

    • DOI

      10.1093/cvr/cvu185

    • NAID

      120005619790

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effects of super-flux (high performance) dialyzer on plasma glycosylated pro-B-type natriuretic peptide (proBNP) and glycosylated N-Terminal proBNP in end-stage renal disease patients on dialysis.2014

    • Author(s)
      Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Nakao K, Minami T, Yamada C, Ueshima K, Ikeda Y, Okamoto H, Horii K, Nagata K, Kangawa K, Minamino N, Nakao K.
    • Journal Title

      PLoS One

      Volume: 25 Issue: 3 Pages: e92314-e92314

    • DOI

      10.1371/journal.pone.0092314

    • NAID

      120007100132

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin II type 1a receptor signalling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy2013

    • Author(s)
      Yasuno, S., Kuwahara, K., Kinoshita, H., Yamada, C., Nakagawa, Y., Usami, S., Kuwabara, Y., Ueshima, K., Harada, M., Nishikimi, T., Nakao, K.
    • Journal Title

      British Journal of Pharmacology

      Volume: 170(7) Issue: 7 Pages: 1384-1395

    • DOI

      10.1111/bph.12328

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression of HCN channels in the ventricular myocardium contributes to enhanced arrhythmicity in mouse failing hearts.2013

    • Author(s)
      Kuwabara, Y., Kuwahara, K., Takano, M., Kinoshita, H., Arai, Y., Yasuno, S., Nakagawa, Y., Igata, S., Usami, S., Minami, T., Yamada, Y., Nakao, K., Yamada, C., Shibata, J., Nishikimi, T., Ueshima, K., Nakao, K.
    • Journal Title

      Journal of the American Heart Association

      Volume: 2(3) Issue: 3

    • DOI

      10.1161/jaha.113.000150

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure2013

    • Author(s)
      Nishikimi, T., Okamoto, H., Nakamura, M., Ogawa, N., Horii, K., Nagata, K., Nakagawa, Y., Kinoshita, H., Yamada, C., Nakao, K., Minami, T., Kuwabara, Y., Kuwahara, K., Masuda, I., Kangawa, K., Minamino, N., Nakao, K.
    • Journal Title

      PLoS ONE

      Volume: 8(1) Issue: 1 Pages: e53233-e53233

    • DOI

      10.1371/journal.pone.0053233

    • NAID

      120005241437

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Increased Expression of HCN channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts2014

    • Author(s)
      Yoshihiro Kuwabara, Koichiro Kuwahara, Makoto Takano, Hideyuki Kinoshita, Yuji Arai, Yasuaki Nakagawa, Shinji Ysuno, Sachiyo Igata, Satoru Usami, Takeya Minami, Yuko Yamada, Kazuhiro Nakao, Chinatsu Yamada, Junko Shibata, Toshio Nishikimi, Kenji Ueshima and Kazuwa Nakao
    • Organizer
      第29回日本不整脈学会・第31回日本心電学会合同学術集会
    • Place of Presentation
      ザ・プリンスパークタワー東京
    • Year and Date
      2014-07-22 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 左室リモデリング進行及び催不整脈性抑制におけるレニンーアンジオテンシン系の検討2013

    • Author(s)
      山田千夏、桑原宏一郎、木下秀之、錦見俊雄、中尾一泰、桒原佳宏、保野慎治、中川靖章、上嶋健治、中尾一和
    • Organizer
      第86回 日本内分泌学会学術総会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺動脈性肺高血圧症に対する新規治療標的としてのTRPC3/6阻害効果の検討2013

    • Author(s)
      木下秀之、桑原宏一郎、清中茂樹、森泰生、赤木達、中村一文、桒原佳宏、中川靖章、錦見俊雄、中尾一和
    • Organizer
      第2回 日本肺循環学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 京都大学大学院医学研究科 内分泌代謝内科学 心臓グループ

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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