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Mst1 promotes progression of dilated cardiomyopathy by modulating immune system

Research Project

Project/Area Number 26461126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MAEJIMA YASUHIRO  東京医科歯科大学, 医学部附属病院, 講師 (40401393)

Co-Investigator(Kenkyū-buntansha) 磯部 光章  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80176263)
Co-Investigator(Renkei-kenkyūsha) SUZUKI JUNICHI  東京大学, 医学系研究科, 特任准教授 (90313858)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords制御性T細胞 / 自己免疫性心筋炎 / リン酸化 / 心筋炎 / 拡張型心筋症 / キナーゼ
Outline of Final Research Achievements

We have previously shown that Mst1 phosphorylates FoxO1, a forehead transcription factor, thereby modulating cell survival of cardiomyocytes through induction of nuclear translocation of FoxO1. In this study, based on this finding, we explored that the role of Mst1 on Foxp3, another forehead transcription factor which regulates the function of regulatory T cell (Treg), and found that Mst1 modulates the progression of post-myocarditis dilated cardiomyopathy through phosphorylating Foxp3 through modulating Treg-mediated immune system.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (30 results)

All 2017 2016 2015 2014

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Acknowledgement Compliant: 4 results,  Open Access: 5 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results)

  • [Journal Article] Projections from single NUCB2/nesfatin-1 neuron in paraventricular nucleus to different brain regions involved in feeding2016

    • Author(s)
      Maejima Y, Kumamoto K, Takenoshita S, Shimomura K
    • Journal Title

      Brain Structure and Function

      Volume: in press Pages: 123-137

    • DOI

      10.1016/j.yjmcc.2016.03.017

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Regulation of autophagy by Beclin 1 in the heart.2016

    • Author(s)
      Maejima Y, Isobe M, Sadoshima J.
    • Journal Title

      J Mol Cell Cardiol

      Volume: 95 Pages: 19-25

    • DOI

      10.1016/j.yjmcc.2015.10.032

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mst1-mediated phosphorylation of Bcl-xL is required for myocardial reperfusion injury.2016

    • Author(s)
      Nakamura M, Zhai P, Del Re DP, Maejima Y, Sadoshima J.
    • Journal Title

      JCI Insight

      Volume: 1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppression of murine autoimmune myocarditis achieved with direct renin inhibition.2016

    • Author(s)
      Takamura C, Suzuki J, Ogawa M, Watanabe R, Tada Y, Maejima Y, Akazawa H, Komuro I, Isobe M.
    • Journal Title

      J Cardiol

      Volume: 68 Issue: 3 Pages: 253-60

    • DOI

      10.1016/j.jjcc.2015.09.008

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent progress in research on molecular mechanisms of autophagy in the heart.2015

    • Author(s)
      Maejima Y, Chen Y, Isobe M, Gustafsson ÅB, Kitsis RN, Sadoshima J.
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 308(4) Issue: 4 Pages: H259-H268

    • DOI

      10.1152/ajpheart.00711.2014

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Endogenous Drp1 Mediates Mitochondrial Autophagy and Protects the Heart Agains Energy Stress.2015

    • Author(s)
      Y. Ikeda, A. Shitakabe, Y. Maejeima, P. Zhai, S. Sciarretta, J. Toli, M. Nomura, K.Mihara, K. Egashira, M. Ohnishi, M. Abdellatif and J. Sadoshima
    • Journal Title

      Circulation Research

      Volume: 116 Issue: 2 Pages: 264-278

    • DOI

      10.1161/circresaha.116.303356

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] mTORC2 regulates cardiac response to stress by inhibiting MST1.2015

    • Author(s)
      Sciarretta S, Zhai P, Maejima Y, Del Re DP, Nagarajan N, Yee D, Liu T, Magnuson MA, Volpe M, Frati G, Li H, Sadoshima J.
    • Journal Title

      Cell Rep

      Volume: 11 Issue: 1 Pages: 125-136

    • DOI

      10.1016/j.celrep.2015.03.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] オートファジー機能異常による心不全発症機構の解明2015

    • Author(s)
      前嶋康浩
    • Journal Title

      東京都医師会雑誌

      Volume: 68 Pages: 588-591

    • Related Report
      2015 Research-status Report
  • [Journal Article] 心不全とオートファジー2015

    • Author(s)
      前嶋康浩
    • Journal Title

      循環器内科

      Volume: 78 Pages: 512-519

    • NAID

      40020657358

    • Related Report
      2015 Research-status Report
  • [Journal Article] MuRF1 negatively regulates pathological cardiac hypertrophy through downregulation of calcineurin A2014

    • Author(s)
      M.Yokota(他8名、7番目) et al
    • Journal Title

      Circ Heart Fail

      Volume: 7 Issue: 3 Pages: 479-490

    • DOI

      10.1161/circheartfailure.113.000713

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL.2014

    • Author(s)
      Del Re DP, Matsuda T, Zhai P, Maejima Y, Jain MR, Liu T, Li H, Hsu CP, Sadoshima J.
    • Journal Title

      Mol Cell

      Volume: 54(4) Issue: 4 Pages: 639-650

    • DOI

      10.1016/j.molcel.2014.04.007

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] SUMOylation: a novel protein quality control modifier in the heart.2014

    • Author(s)
      Maejima Y, Sadoshima J.
    • Journal Title

      Circ Res

      Volume: 115(8) Issue: 8 Pages: 686-689

    • DOI

      10.1161/circresaha.114.304989

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] The Critical Role of Autophagy in the Progression of Heart Failure.2017

    • Author(s)
      前嶋康浩
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] オートファジーの制御異常による心不全発症機構の解明2017

    • Author(s)
      前嶋康浩
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Suppression of dipeptidyl peptidase-4 activity attenuates cardiac dysfunction during autoimmune myocarditis by suppressing cathepsin-G activity2016

    • Author(s)
      Maejima Y, Ito Y, Tamura N, Watanabe R, Isobe M
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 報告:わが国の心臓移植の現状2016

    • Author(s)
      前嶋康浩
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 炎症を基盤とした拡張型心筋症に対するリナグリプチンの発症および病状進展抑制効果に関する機序についての研究2016

    • Author(s)
      前嶋康浩
    • Organizer
      第20回日本適応医学会学術集会
    • Place of Presentation
      東京コンベンションホール(東京都中央区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] GSK-3β inhibits cardiac hypertrophy by phosphorylating FoxO12016

    • Author(s)
      Yasuhiro Maejima
    • Organizer
      American Heart Association Scientific Sessions 2016
    • Place of Presentation
      Ernest N. Morial Convention CenTer(New Orleans, Louisiana, USA)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GSK3β alleviates cardiac hypertrophy and LV dysfunction through modulation of FoxO1 activity in response to pressure overload2016

    • Author(s)
      Yasuhiro Maejima
    • Organizer
      第20回日本心不全学会学術集会
    • Place of Presentation
      ロイトン札幌(北海道札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Critical role for dipeptidyl peptidase-4 activity the pathogenesis of experimental autoimmune myocarditis2016

    • Author(s)
      Yasuhiro Maejima
    • Organizer
      Basic Cardiovascular Sciences 2016 Scientific Sessions of American Heart Association
    • Place of Presentation
      Hyatt Regency Phoenix(Phoenix, Arizona, USA)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dipeptidyl peptidase-4 deteriorates cardiac function during autoimmune myocarditis by facilitating cathepsin-G activity2015

    • Author(s)
      Maejima Y, Ito Y, Tamura N, Watanabe R, Isobe M
    • Organizer
      American Heart Association Scientific Sessions 2015
    • Place of Presentation
      Orlando (USA)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高安動脈炎の感受性遺伝子MLXの一塩基多型による発症・病態進展機転への関与についての検討2015

    • Author(s)
      前嶋康浩
    • Organizer
      第56回日本脈管学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2015-10-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Dipeptidyl peptidase-4 suppression leads to attenuation of cardiac dysfunction caused by autoimmune myocarditis through inhibiting cathepsin-G activity2015

    • Author(s)
      Maejima Y, Ito Y, Tamura N, Watanabe R, Isobe M
    • Organizer
      第19回日本心不全学会学術集会
    • Place of Presentation
      グランフロント大阪(大阪府大阪市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Single nucleotide polymorphism of MLX gene plays a crucial role in the pathogenesis of Takayasu Arteritis through facilitating inflammasome formation of the aorta2015

    • Author(s)
      Maejima Y, Tamura N, Isobe M
    • Organizer
      Basic Cardiovascular Sciences 2015 Scientific Sessions of American Heart Association 2015
    • Place of Presentation
      New Orleans (USA)
    • Year and Date
      2015-07-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mammalian Sterile 20-like Kinase-1 Inhibits Autophagy, Thereby Compromising Protein Quality Control in the Heart2015

    • Author(s)
      前嶋康浩
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Suppression of autophagy by Mst1 exacerbates cardiac dysfunction by deteriorating protein quality control in the heart.2014

    • Author(s)
      前嶋康浩
    • Organizer
      第31回国際心臓研究学会(ISHR)日本部会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-11-29
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Dynamin-related protein 1 (Drp1) accumulates in mitochondria and plays a protective role in the heart in response to pressure overload.2014

    • Author(s)
      Maejima Y, Shirakabe A, Ikeda Y, Zhai P, Sadoshima J.
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Mst1 plays a protective role in response to ischemia in the heart by promoting C/EBP-β activation.2014

    • Author(s)
      Maejima Y, Nagarajan N, Zhai P, Isobe M, Sadoshima J.
    • Organizer
      American Heart Association Scientific Sessions 2014
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Mst1 plays a cell-protective role in the heart through FoxO1 and C/EBP-β phosphorylation.2014

    • Author(s)
      Maejima Y, Sadoshima J, Isobe M.
    • Organizer
      第18回日本心不全学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-10
    • Related Report
      2014 Research-status Report
  • [Presentation] オートファジー機能異常による心不全発症機構の解明2014

    • Author(s)
      前嶋康浩
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2014-07-04
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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