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The molecular and cellular mechanism of myocardial repair/regeneration

Research Project

Project/Area Number 26293054
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General pharmacology
Research InstitutionOsaka University

Principal Investigator

FUJIO Yasushi  大阪大学, 薬学研究科(研究院), 教授 (20359839)

Co-Investigator(Kenkyū-buntansha) 毛利 友美  大阪大学, 薬学研究科(研究院), 研究員 (20572960)
中山 博之  大阪大学, 薬学研究科(研究院), 准教授 (40581062)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords心臓 / 組織修復・再生 / 心筋細胞増殖 / 細胞骨格 / 心筋炎 / STAT3 / 循環器・高血圧 / 心筋組織修復 / 炎症 / サイトカイン / Moesin / 心血管・血液 / 心筋 / 再生
Outline of Final Research Achievements

As mammalian cardiomyocytes substantially cease to proliferate immediately after birth, it has been believed that adult mammalian hearts show only limited regenerative capacities. However, clinically, most cases of acute myocarditis are self-limiting with myocardial recovery. Thus, we hypothesized that adult cardiomyocytes might restore regenerative activities during the healing process of myocarditis. In this study, using experimental autoimmune myocarditis (EAM) model, we addressed this hypothesis from two viewpoints; One is phenotypic modulation of cardiomyocytes and the other is cardiomyocyte proliferation. As for phenotypic modulation, proteomics analysis revealed that the expression of moesin, a cytoskeletal protein, was upregulated in cardiomyocytes, leading to the protrusion formation. As for cell proliferation, we detected cell cycle marker-positive cardiomyocytes at the beginning of the myocardial recovery, proposing the unexpected adult cardiomyocyte proliferation.

Report

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

    (33 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 9 results,  Acknowledgement Compliant: 3 results) Presentation (22 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results)

  • [Journal Article] A mouse model of Epstein-Barr virus LMP1 and LMP2A driven germinal center B-cell lymphoproliferative disease.2017

    • Author(s)
      1Minamitani, T., Ma, Y., Zhou, H., Kida, H., Tsai, C.-Y., Obana, M., Okuzaki, D., Fujio, Y., Kumanogoh, A., Kikutani, H., Zhao, B., Kieff, E., Gewuz, B. E., Yasui, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 印刷中 Issue: 18 Pages: 4751-4756

    • DOI

      10.1073/pnas.1701836114

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adult murine cardiomyocytes exhibit regenerative activity with cell cycle reentry through STAT3 in the healing process of myocarditis.2017

    • Author(s)
      Miyawaki, A., Obana, M., Mitsuhara, Y., Orimoto, A., Nakayasu, Y., Yamashita, T., Fukada, S., Maeda, M., Nakayama, H., Fujio, Y.
    • Journal Title

      Sci. Rep.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Caveolae-specific activation loop between CaMKII and L-type Ca2+ channel aggravates cardiac hypertrophy in α1 adrenergic stimulation.2017

    • Author(s)
      Tonegawa, K., Otsuka, W., Kumagai, S., Matsunami, S., Hayamizu, N., Tanaka, S., Moriwaki, K., Obana, M., Maeda, M., Asahi, M., Kiyonari, H., Fujio, Y., Nakayama, H.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol.

      Volume: 312 Issue: 3 Pages: H501-H514

    • DOI

      10.1152/ajpheart.00601.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phospholamban inhibition by a single dose administration of locked nucleic acid antisense oligonucleotide improves cardiac contractility in pressure overload-induced systolic dysfunction in mice.2017

    • Author(s)
      Morihara, H., Yamamoto, T., Oiwa, H., Tonegawa, K., Tsuchiyama, D., Kawakatsu, I., Obana, M., Maeda, M., Mohri, T., Obika, S., Fujio, Y., Nakayama, H.
    • Journal Title

      J. Cardiovasc. Pharmacol. Ther.

      Volume: 印刷中 Issue: 3 Pages: 273-282

    • DOI

      10.1177/1074248416676392

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Moesin is activated in cardiomyocytes in experimental autoimmune myocarditis and mediates cytoskeletal reorganization with protrusion formation2016

    • Author(s)
      Akimitsu Miyawaki, Yusuke Mitsuhara, Aya Orimoto, Yusuke Nakayasu, Shin-ichi Tsunoda, Masanori Obana, Makiko Maeda, Hiroyuki Nakayama, Yasuo Yoshioka, Yasuo Tsutsumi, Yasushi Fujio
    • Journal Title

      The American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 311 Issue: 2 Pages: 476-486

    • DOI

      10.1152/ajpheart.00180.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Four cases of investigational therapy with interleukin-11 against acute myocardial infarction.2016

    • Author(s)
      Nakagawa, M., Owada Y., Izumi, Y., Nonin, S., Sugioka, K., Nakatani, D., Iwata, S., Mizutani, K., Nishimura, S., It, A., Fujita, S., Daimon, T., Sawa, Y., Asakura, M., Maeda, M., Fujio, Y., Yoshiyama, M.
    • Journal Title

      Heart and Vessels

      Volume: 31 Issue: 9 Pages: 1574-1578

    • DOI

      10.1007/s00380-015-0788-4

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myeloid cell-derived LRG attenuates adverse cardiac remodeling after myocardial infarction.2016

    • Author(s)
      Kumagai, S., Nakayama, H., Fujiomoto, M., Honda, H., Serada, S., Ishibashi-Ueda, H., Kasai, A., Obana, M., Sawa, Y., Fujio, Y., Naka, T.
    • Journal Title

      Cardiovasc. Res.

      Volume: 109 Issue: 2 Pages: 272-282

    • DOI

      10.1093/cvr/cvv273

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Four cases of investigational therapy with interleukin-11 against acute myocardial infarction.2016

    • Author(s)
      Nakagawa, M., Owada Y., Izumi, Y., Nonin, S., Sugioka, K., Iwata, S., Mizutani, K., Nishimura, S., It, A., Fujita, S., Daimon, T., Sawa, Y., Asakura, M., Maeda, M., Fujio, Y., Yoshiyama, M.
    • Journal Title

      Heart and Vessels

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac specific ablation of STAT3 gene in subacute phase of myocardial infarction exacerbated cardiac remodeling.2015

    • Author(s)
      Enomoto, D., Obana, M., Miyawaki, A., Maeda, M., Nakayama, H., Fujio, Y.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol.

      Volume: 309 Issue: 3 Pages: H471-H480

    • DOI

      10.1152/ajpheart.00730.2014

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells.2015

    • Author(s)
      Tanaka, T., Obana, M., Mohri, T., Maeda, M., Fujio, Y.
    • Journal Title

      Cytokine

      Volume: 75 Issue: 2 Pages: 365-372

    • DOI

      10.1016/j.cyto.2015.06.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Inhibition of N-Glycosylation of Glycoprotein 130 Molecule Abolishes STAT3 Activation by IL-6 Family Cytokines in Cultured Cardiac Myocytes.2014

    • Author(s)
      Matsuo R, Morihara H, Mohri T, Murasawa S, Takewaki K, Nakayama H, Maeda M, Fujio Y.
    • Journal Title

      PLoS One

      Volume: 23 Issue: 10 Pages: e111097-e111097

    • DOI

      10.1371/journal.pone.0111097

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 急性心筋梗塞に対するヒトIL-11製剤を用いた心筋保護治療2017

    • Author(s)
      藤尾慈、前田真貴子、大門貴志、中谷大作、杉岡憲一、岩田真一、澤芳樹、朝倉正紀、泉康雄、葭山稔
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎県長崎市
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] eIF4Bは、Pim-1キナーゼの下流における心筋細胞保護因子である2017

    • Author(s)
      横山由加里 松本浩太朗 木下真希 尾花理徳 前田真貴子 中山博之 藤尾慈
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎県長崎市
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] RORgammatのヘテロ欠損は心筋梗塞後の心筋リモデリングを悪化させる2017

    • Author(s)
      榎本大智 尾花理徳 松本浩太朗 前田真貴子 中山博之 藤尾慈
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎県長崎市
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 骨髄細胞特異的Runx2の欠損は心筋梗塞後の心筋リモデリングを悪化させる2017

    • Author(s)
      芦塚萌 熊谷渉平  柳瀬絵美子 松本浩太朗 尾花理徳 前田真貴子 中山博之 藤尾慈
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎県長崎市
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Moesinは実験的自己免疫性心筋炎モデルにおいて活性化し、仮足形成を伴う組織修復に関与する2017

    • Author(s)
      密原佑介 宮脇昭光 折本彩 中安祐介 角田慎一 尾花理徳 前田真貴子 中山博之 吉岡靖雄 堤康央  藤尾慈
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎県長崎市
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Heterozygous ablation of RORγt gene deteriorates adverse cardiac remodeling after myocardial infarction.2016

    • Author(s)
      Enomoto, D., Obana, M., Matsumoto, K., Sakata, Y., Maeda, M., Nakayama, H., Fujio, Y.
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      New Orleans. USA.
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Myeloid cell-specific Runx2 deficiency exacerbates adverse cardiac remodeling after myocardial infarction.2016

    • Author(s)
      Ashizuka, M., Kumagai, S., Yanase, E., Obana, M., Maeda, M., Sakata, Y., Nakayama, H., Fujio, Y.
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      New Orleans. USA.
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fibroblast-specific beta2 adrenergic receptor signaling regulates cardiac hypertrophy in mice.2016

    • Author(s)
      Tonegawa, K., Tanaka, S., Takahashi, M., Fuchigami, S., Obana, M., Maeda, M., Sakata, Y., Fujio, Y,. Nakayama, H.
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      New Orleans. USA.
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Adult mammalian hearts restore intrinsic regenerative capacity through signal transducer and activator of transcription 3 in the resolution phase of myocarditis.2016

    • Author(s)
      Miyawaki, A., Obana, M., Mitsuhara, Y., Orimoto, A., Nakayasu, Y., Yamashita, T., Fukada, S., Maeda, M., Sakata, Y., Nakayama, H., Fujio, Y.
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      New Orleans. USA.
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 心筋炎病態下におけるSTAT3を介した成体心筋細胞増殖2016

    • Author(s)
      宮脇昭光 高家圭紀 密原佑介 山下朋美 尾花理徳 前田真貴子 中山博之 藤尾慈
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Myeloid Cell Derived Leucine Rich α2 Glycoprotein Attenuates AdverseCardiac Remodeling After Myocardial Infarction.2015

    • Author(s)
      Shohei Kumagai, Hiroyuki Nakayama, Minoru Fujimoto, Hiromi Honda, Satoshi Serada, Atsushi Kasai, Masanori Obana, Yasushi Sakata, Yoshiki Sawa, Tetsuji Naka, Yasushi Fujio
    • Organizer
      American Heart Association Scientific Sessions 2015
    • Place of Presentation
      Orlando
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Blockade of NKG2D/NKG2D Ligands Interaction Attenuated Cardiac Remodeling after Myocardial Infarction2015

    • Author(s)
      Kotaro Matsumoto, Masanori Obana, Rina Hashidzume, Yukari Yokoyama,Nakayama, Shigeru Miyagawa, Tomomi Mohri, Makiko Maeda, Yasushi Sakata, Hiroyuki Nakayama, Yoshiki Sawa, Yasushi Fujio
    • Organizer
      American Heart Association Scientific Sessions 2015
    • Place of Presentation
      Orlando
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cardiac STAT3 activation in subacute phase of myocardial infarction was required for the suppression of adverse cardiac remodeling2015

    • Author(s)
      Daichi Eonomoto, Masanori Obana, Akimitsu Miyawaki, Makiko Maeda, Hiroyuki Nakayama, Yasushi Fujio
    • Organizer
      American Heart Association Scientific Sessions 2015
    • Place of Presentation
      Orlando
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] gp130サイトカインと心血管病2015

    • Author(s)
      藤尾 慈、前田真貴子、朝倉正紀、中谷大作、泉 康雄、葭山 稔
    • Organizer
      第1回国際心血管薬物療法学会日本部会
    • Place of Presentation
      京都 ハイアットリージェンシー京都
    • Year and Date
      2015-06-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Interleukin 27 induces endothelial differentiation in murine cardiac stem cells2015

    • Author(s)
      田中智大、尾花理徳、前田真貴子、中山博之、藤尾慈
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Elucidation of molecular mechanism of cardiomyocyte necrosis induced by reactive oxygen species.2015

    • Author(s)
      土山大介、中山博之、森原啓文、石田瑛子、尾花理徳、前田真貴子、藤尾慈
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] IL-27 negatively regulates murine experimental autoimmune myocarditis (EAM).2015

    • Author(s)
      古谷知佳、宮脇昭光、大谷勇太、尾花理徳、前田真貴子、中山博之、藤尾慈
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Adrenergic receptors β2 and β3 transduce differential signalsin cardiac fibroblasts.2015

    • Author(s)
      五十嵐裕美、中山博之、松浪佐知、早水菜穂、舎川洸太、尾花理徳、前田真貴子、藤尾慈
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] The properties of cardiac Sca-1+ resident stem cells are altered in response to myocardial inflammation.2015

    • Author(s)
      松原由実、宮脇昭光、榎原正貴、尾花理徳、前田真貴子、中山博之、藤尾慈
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Caveolae-specific phosphorylation of L-type calcium channel b2a subunit exaggerates cardiac hypertrophic responses after a1 adrenergic stimulation in mice2014

    • Author(s)
      Hiroyuki Nakayama, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu, Kota Tonegawa, Wataru Otsuka, Yasushi Fujio
    • Organizer
      International Society of Heart Research 日本部会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Caveolae-specific phosphorylation of L-type calcium channel beta2a subunit excerbates cardiac hypertrophy2014

    • Author(s)
      Shohei Kumagai, Hiroyuki Nakayama, Nao Hayamizu, Wataru Otsuka, Yasushi Fujio
    • Organizer
      American Heart Association, Scientific Sessions 2014
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Caveolae-specific phosphorylation of L-type calcium channel b2a subunit exaggerates cardiac hypertrophic responses after a1 adrenergic stimulation in mice.2014

    • Author(s)
      Hiroyuki Nakayama, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu, Kota Tonegawa, Wataru Otsuka , Yasushi Fujio
    • Organizer
      American Heart Association, Basic Cardiovascular Sciences
    • Place of Presentation
      Las Vegas, USA
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Annual Research Report

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

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