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Roles of extracellular environment and various cells carrying different function for cardiac fibrosis

Research Project

Project/Area Number 25253011
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionKyushu University

Principal Investigator

KUROSE HITOSHI  九州大学, 薬学研究院, 教授 (10183039)

Co-Investigator(Kenkyū-buntansha) 仲矢 道雄  九州大学, 薬学研究科(研究院), 准教授 (80464387)
長坂 明臣  九州大学, 薬学研究科(研究院), 助教 (10723877)
Project Period (FY) 2013-10-21 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2016: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2015: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2014: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2013: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Keywords筋線維芽細胞 / 心筋梗塞 / 死細胞 / 抗炎症作用 / 免疫細胞 / 線維芽細胞 / 貪食 / 炎症 / 線維化 / 薬理学 / シグナル伝達 / 循環器・高血圧 / 免疫学 / 細胞外微小環境
Outline of Final Research Achievements

Heart often develops heart failure after myocardial infarction, if proper revascularization is not provided. Inflammatory responses are believed to be a factor to progress to heart failure after myocardial infarction. As inflammation is induced by the cellular components released from dead cells, the quick and efficient removal of dead cells in myocardial infarction is important for preventing the development of heart failure. So far, phagocytes such as macrophages and dendritic cells infiltrating infarct area are supposed to be the players of removing dead cells. In this study, myofibroblasts remove dead cell as well as phagocytes do. The removal of dead cells by myofibroblasts requires MFG-E8 that bridges between apoptotic cells and phagocytes. Thus, myofibroblasts remove dead cells after myocardial infarction, and suppress the progression to heart failure.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (33 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 9 results,  Acknowledgement Compliant: 6 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] Dr. Nebigil CG./University of Strasbourg(France)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] β-Adrenergic Receptor and Insulin Resistance in the Heart.2017

    • Author(s)
      Mangmool S, Denkaew T, Parichatikanond W, Kurose H.
    • Journal Title

      Biomol Ther (Seoul).

      Volume: 25 Issue: 1 Pages: 44-56

    • DOI

      10.4062/biomolther.2016.128

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction.2017

    • Author(s)
      Michio Nakaya,Kenji Watari,Mitsuru Tajima,Takeo Nakaya,Shoichi Matsuda,Hiroki Ohara,Hiroaki Nishihara,Hiroshi Yamaguchi,Akiko Hashimoto,Mitsuho Nishida,Akiomi Nagasaka,Yuma Horii,Hiroki Ono,Gentaro Iribe,Ryuji Inoue,Makoto Tsuda,Kazuhide Inoue,Akira Tanaka,Masahiko Kuroda,Shigekazu Nagata,Hitoshi Kurose
    • Journal Title

      Journal of Clinical Investigation

      Volume: 127 Issue: 1 Pages: 383-401

    • DOI

      10.1172/jci83822

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Myofibroblasts and inflammatory cells as players of cardiac fibrosis.2016

    • Author(s)
      Kurose H, Mangmool S.
    • Journal Title

      Arch Pharm Res.

      Volume: 39 Issue: 8 Pages: 1100-1113

    • DOI

      10.1007/s12272-016-0809-6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification of a Potent and Selective GPR4 Antagonist as a Drug Lead for the Treatment of Myocardial Infarction2016

    • Author(s)
      Hayato Fukuda, Saki Ito, Kenji Watari, Chihiro Mogi, Mitsuhiro Arisawa, Fumikazu Okajima, Hitoshi Kurose, Satoshi Shuto
    • Journal Title

      ACS Med. Chem. Lett.

      Volume: 7 Issue: 5 Pages: 493-497

    • DOI

      10.1021/acsmedchemlett.6b00014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The purinergic P2Y6 receptor heterodimerizes with the angiotensin AT1 receptor to promote angiotensin II-induced hypertension2016

    • Author(s)
      A. Nishimura, C. Sunggip, H. Tozaki-Saitoh, T. Shimauchi, T. Numaga-Tomita, K. Hirano, T. Ide, J-M. Boeynaems, H. Kurose, M. Tsuda, B. Robaye, K. Inoue and M. Nishida
    • Journal Title

      Science Signaling

      Volume: Jan 19;9(411) Issue: 411

    • DOI

      10.1126/scisignal.aac9187

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A new approach of indirect enzyme-linked immunosorbent assay for determination of D-glutamic acid through in situ conjugation2016

    • Author(s)
      Sakamoto, S., Nagamitsu, R., Matsuura, Y., Tsuneura, Y., Kurose, H., Tanaka, H.*, Morimoto, S.
    • Journal Title

      Journal of Immunoassay and Immunochemistry

      Volume: 37 Issue: 3 Pages: 296-306

    • DOI

      10.1080/15321819.2015.1135161

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery and cardioprotective effects of the first non-Peptide agonists of the g protein-coupled prokineticin receptor-1.2015

    • Author(s)
      Gasser A, Brogi S, Urayama K, Nishi T, Kurose H, Tafi A, Ribeiro N, Désaubry L, Nebigil CG.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 4 Pages: e0121027-e0121027

    • DOI

      10.1371/journal.pone.0121027

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GRK6 phosphorylates IκBα at Ser32/Ser36 and enhances TNF-α-induced inflammation2015

    • Author(s)
      Yuki Ohba, Michio Nakaya*, Kenji Watari, Akiomi Nagasaka, & Hitoshi Kurose.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 461 Issue: 2 Pages: 307-313

    • DOI

      10.1016/j.bbrc.2015.04.027

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of imidazopyridine compounds as negative allosteric modulators of proton-sensing GPR4 in extracellular acidification-induced responses2015

    • Author(s)
      Ayaka Tobo, Masayuki Tobo, Takashi Nakakura, Masashi Ebara, Hideaki Tomura, Chihiro Mogi, Dong-Soon Im, Naoya Murata, Atsushi Kuwabara, Saki Ito, Hayato Fukuda, Mitsuhiro Arisawa, Satoshi Shuto, Michio Nakaya, Hitoshi Kurose, Koichi Sato, Fumikazu Okajima
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 6 Pages: e0129334-e0129334

    • DOI

      10.1371/journal.pone.0129334

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification of a new molecule that promotes clearance of apoptotic cells — G protein-coupled receptor kinase 6 is involved in engulfment of apoptotic cells2015

    • Author(s)
      仲矢道雄、黒瀬等
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 145 Issue: 1 Pages: 14-20

    • DOI

      10.1254/fpj.145.14

    • NAID

      130004827709

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple functions of G protein-coupled receptor kinases2014

    • Author(s)
      Watari K, Nakaya M, Kurose H
    • Journal Title

      Journal of Molecular Signaling

      Volume: 9 Pages: 1-1

    • DOI

      10.1186/1750-2187-9-1

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Attenuated desensitization of -adrenergic receptor by water-soluble N-nitrosamines that induce S-nitrosylation without nitric oxide release.2013

    • Author(s)
      Makita N, Kabasawa Y, Otani Y, Firman F, Sato J, Hashimoto M, Nakaya M, Nishihara H, Nangaku M, Kurose H, Ohwada T and Iiri T.
    • Journal Title

      Circ. Res.

      Volume: 112 Pages: 327-334

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiple signaling routes involved in the regulation of adenylyl cyclase and extracellular regulated kinase by dopamine D(2) and D(3) receptors.2013

    • Author(s)
      Jin M, Min C, Zheng M, Cho DI, Cheong SJ, Kurose H, Kim KM.
    • Journal Title

      Pharmacol. Res.

      Volume: 67 Pages: 31-41

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Regulatory Function of Sweet Taste-Sensing Receptor in Adipogenic Differentiation of 3T3-L1 Cells.2013

    • Author(s)
      Masubuchi Y, Nakagawa Y, Ma J, Sasaki T, Kitamura T, Yamamoto Y, Kurose H, Kojima I, Shibata H.
    • Journal Title

      PLoS ONE

      Volume: 8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: involvement of Ric-8B in Gs suppression by Gq signal.2013

    • Author(s)
      Jenie RI, Nishimura M, Fujino M, Nakaya M, Mizuno N, Tago K, Kurose H, Itoh H.
    • Journal Title

      Genes Cells

      Volume: 18 Pages: 1095-1106

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 心肥大時に生じる死細胞はMFG-E8を介して貪食除去される2017

    • Author(s)
      松田翔一、仲矢道雄、小宮詩織、長坂明臣、黒瀬等
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台市仙台国際センター、東北大学川内北キャンパス
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] BLT1は心筋梗塞時における炎症を悪化させる2017

    • Author(s)
      堀井雄真、仲矢道雄、西原弘朗、大原広貴、渡健治、長坂明臣、黒瀬等
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホール アストピア
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] The role of GRK2 in BMP signaling2017

    • Author(s)
      Yuki Ohba, Michio Nakaya, Akiomi Nagasaka, Hitoshi Kurose
    • Organizer
      International Students' Science Camp of Kyushu University KAIST-Kyushu University Joint Seminar
    • Place of Presentation
      Shikanoshima, Fukuoka
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 心肥大時に生じる死細胞はMFG-E8を介して除去される2016

    • Author(s)
      松田翔一、仲矢道雄、小宮詩織、長坂明臣、黒瀬等
    • Organizer
      第15回 次世代を担う若手ファーマ・バイオフォーラム2016
    • Place of Presentation
      大阪大学吹田地区薬学キャンパス
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心筋梗塞時の死細胞を除去するメカニズム2016

    • Author(s)
      仲矢道雄、渡健治、黒瀬等
    • Organizer
      第15回生命科学研究会
    • Place of Presentation
      メルパルク東京
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心筋梗塞時にGタンパク質共役型受容体によって仲介される応答2016

    • Author(s)
      黒瀬等
    • Organizer
      第89回 日本薬理学会年会
    • Place of Presentation
      横浜パシフィコ(神奈川)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 心筋梗塞におけるpH感知性GPCR(TDAG8)の役割解析2015

    • Author(s)
      西俊英、長坂明臣、小野達貴、仲矢道雄、黒瀬等
    • Organizer
      第14回 生命科学研究会
    • Place of Presentation
      三浦市民ホール(三浦市三崎、神奈川)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 心筋梗塞時におけるプロトン感知性受容体(TDAG8)の役割解明2015

    • Author(s)
      西俊英、長坂明臣、仲矢道雄、岡島史和、黒瀬等
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] βアレスチンを介したバイアス型シグナリング2015

    • Author(s)
      黒瀬等
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 心肥大時に生じるアポトーシス細胞はMFG-E8を介して除去される2014

    • Author(s)
      松田翔一、仲矢道雄、小宮詩織、長坂明臣、黒瀬等
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      産業医科大学ラマツィーニホール、福岡
    • Year and Date
      2014-11-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] The Physiological and pathological roles of cardiac fibroblasts2014

    • Author(s)
      黒瀬等、仲矢道雄
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館、京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 心肥大におけるMFG-E8の役割解明2014

    • Author(s)
      松田翔一、仲矢道雄、小宮詩織、長坂明臣、黒瀬等
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2014
    • Place of Presentation
      大阪、近畿大学
    • Year and Date
      2014-08-30 – 2014-08-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] 心筋梗塞時に生じる炎症応答における線維芽細胞の役割2014

    • Author(s)
      黒瀬等、仲矢道雄
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学 郡元キャンパス
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] β-アレスチン2による心筋梗塞後の炎症応答抑制メカニズムの解明2013

    • Author(s)
      渡健治、仲矢道雄、黒瀬等
    • Organizer
      第66回 日本薬理学会西南部会
    • Place of Presentation
      福岡大学薬学部
    • Related Report
      2013 Annual Research Report
  • [Book] バイアス型シグナル2016

    • Author(s)
      黒瀬等
    • Total Pages
      6
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2015 Annual Research Report
  • [Book] βアドレナリン受容体2016

    • Author(s)
      黒瀬等
    • Total Pages
      7
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2015 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://chudoku.phar.kyushu-u.ac.jp/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2013-10-24   Modified: 2019-07-29  

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