• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of EPRAP on the pathophysiology of chronic inflammatory diseases

Research Project

Project/Area Number 26460338
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionKyoto University

Principal Investigator

MINAMI Manabu  京都大学, 医学研究科, 講師 (90511907)

Co-Investigator(Renkei-kenkyūsha) SENO Hiroshi  京都大学, 大学院医学研究科, 教授 (90335266)
Research Collaborator NAKATSUJI Masato  
YASUI Mika  
FUJIKAWA Risako  
HIGUCHI Sei  
FUKUMITSU Ryu  
IKEDO Taichi  
NAGATA Manabu  
HAYASHI Kosuke  
MIYATA Takeshi  
YANG Tao  
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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsEPRAP / マクロファージ / 慢性炎症 / シグナル情報伝達 / 翻訳後修飾 / シグナル情報伝達系
Outline of Final Research Achievements

EP4 receptor-associated protein, EPRAP, has been identified as a novel cytoplasmic regulator of macrophage activation, which inhibits MEK-ERK pathway activation induced by inflammatory stimuli. In this study, we aimed to dissect the significance and pathophysiological roles of EPRAP on chronic inflammation in vivo. We generated EPRAP-deficient mice as well as transgenic mice with enforced expression of EPRAP in macrophages, and created various animal models of chronic inflammatory diseases. Our study demonstrated that EPRAP deficiency markedly worsened the inflammatory phenotypes and outcomes of inflammatory bowel disease and pulmonary fibrosis. Our results indicated that EPRAP plays crucial roles in the pathogenesis of chronic inflammatory diseases; and EP4-EPRAP signaling could be a novel diagnostic or therapeutic target for refractory chronic diseases.

Report

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

    (23 results)

All 2017 2016 2015 2014 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Deficiency in EP4 receptor-associated protein ameliorates abnormal anxiety-like behavior and brain inflammation in a mouse model of Alzheimer’s disease.2017

    • Author(s)
      Fujikawa R, S. Higuchi, M. Nakatsuji, M. Yasui, T. Ikedo, M. Nagata, K. Hayashi, M. Yokode, M. Minami.
    • Journal Title

      Am J Pathol.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] EP4 receptor-associated protein in microglia promotes inflammation in the brain2016

    • Author(s)
      (1)Risako Fujikawa, Sei Higuchi, Masato Nakatsuji, Mika Yasui, Taichi Ikedo, Manabu Nagata, Masayuki Yokode, and Manabu Minami.
    • Journal Title

      American Journal of Pathology

      Volume: 186 Issue: 8 Pages: 1982-1988

    • DOI

      10.1016/j.ajpath.2016.04.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EP4 Receptor-Associated Protein in Macrophages Protects against Bleomycin-Induced Pulmonary Inflammation in mice2016

    • Author(s)
      (2)Higuchi S, Fujikawa R, Ikedo T, Hayashi K, Yasui M, Nagata M, Nakatsuji M, Yokode M and Minami M.
    • Journal Title

      The Journal of Immunology

      Volume: 197 Issue: 11 Pages: 4436-4443

    • DOI

      10.4049/jimmunol.1502618

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety and Anti-tumor Activity of Anti–PD-1 Antibody (Nivolumab: ONO-4538/BMS-936558) in Patients with Platinum-resistant Ovarian Cancer.2015

    • Author(s)
      Hamanishi, J., M. Mandai, T. Ikeda, M. Minami, A. Kawaguchi, T. Murayama, M. Kanai, Y. Mori, S. Matsumoto, S. Chikuma, N. Matsumura, K. Abiko, T. Baba, K. Yamaguchi, A. Ueda, Y. Hosoe, S. Morita, M. Yokode, A. Shimizu, T. Honjo, I. Konishi.
    • Journal Title

      J Clin Oncol

      Volume: 33 Issue: 34 Pages: 4015-22

    • DOI

      10.1200/jco.2015.62.3397

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Prostaglandin E2 Receptor EP4 Regulates Obesity-related Inflammation and Insulin Sensitivity.2015

    • Author(s)
      Yasui, M., Y. Tamura, M. Minami*, S. Higuchi, R. Fujikawa, T. Ikedo, M. Nagata, H. Arai, T. Murayama, and M. Yokode.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 8 Pages: e0136304-e0136304

    • DOI

      10.1371/journal.pone.0136304

    • NAID

      120005678204

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] EP4 receptor–associated protein in macrophages ameliorates colitis and colitis-associated tumorigenesis.2015

    • Author(s)
      Nakatsuji, M., M. Minami*, H. Seno*, M. Yasui, H. Komekado, S. Higuchi, R. Fujikawa, Y. Nakanishi, A. Fukuda, K. Kawada, Y. Sakai, T. Kita, P. Libby, H. Ikeuchi, M. Yokode, and T. Chiba
    • Journal Title

      PLoS Genet

      Volume: 11 Issue: 10 Pages: e1005542-e1005542

    • DOI

      10.1371/journal.pgen.1005542

    • NAID

      120005947032

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Expression of Vasohibin-1 in Human Carotid Atherosclerotic Plaque.2015

    • Author(s)
      Fukumitsu R, Minami M, Yoshida K, Nagata M, Yasui M, Higuchi S, Fujikawa R, Ikedo T, Yamagata S, Sato Y, Arai H, Yokode M, Miyamoto S.
    • Journal Title

      J Atheroscler Thromb.

      Volume: 印刷中

    • NAID

      130005099293

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] EPRAP in microglia promotes inflammation via MKK4-mediated signaling pathway2017

    • Author(s)
      藤川 理沙子、樋口 聖、南 学、安井 美加、池堂 太一、永田 学、横出 正之
    • 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、長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] EPRAP欠損マウスは精神疾患様の行動異常を示す2017

    • Author(s)
      藤川 理沙子、南 学、横出 正之
    • Organizer
      第26回神経行動薬理若手研究者の集い
    • Place of Presentation
      福大メディカルホール(福岡、福岡市)
    • Year and Date
      2017-03-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Onco-Cardiologyの国内外の現状と早期診断におけるバイオマーカーの有用性2016

    • Author(s)
      南 学
    • Organizer
      第64回日本心臓病学会
    • Place of Presentation
      東京国際フォーラム(東京、千代田区)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵臓マクロファージによる膵β細胞の慢性炎症におけるEP4シグナルの役割2015

    • Author(s)
      安井 美加、南 学、橫出 正之
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会合同大会(BMB2015)
    • Place of Presentation
      神戸国際会議場 (神戸・兵庫)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] EP4 receptor–associated protein (EPRAP) deficient mice exhibited behavioral abnormalities.2015

    • Author(s)
      Fujikawa, R., M. Minami, S. Higuchi, M. Yasui, T. Ikedo, M. Nagata, M. Yokode
    • Organizer
      Neuroscience 2015 (Annual Meeting of Society for Neuroscience)
    • Place of Presentation
      Chicago (USA)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミクログリアのEPRAPは炎症を促進する2015

    • Author(s)
      藤川理沙子、南 学、樋口 聖、横出 正之
    • Organizer
      第17回ブレインサイエンス研究会
    • Place of Presentation
      休暇村志賀島 (福岡・福岡)
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
  • [Presentation] EP4受容体活性化による2型糖尿病マウスのインスリン抵抗性改善機構2015

    • Author(s)
      安井 美加、南 学、橫出 正之
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関 (下関・山口)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 薬剤性心毒性の臨床的重要性2015

    • Author(s)
      南 学
    • Organizer
      第79回日本循環器学会
    • Place of Presentation
      大阪国際会議場 (大阪・大阪)
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] マクロファージのEP4受容体関連タンパクEPRAPは糖新生を調節する2015

    • Author(s)
      樋口 聖, 南 学, 藤川 理沙子, 安井美加, 池堂太一, 永田学, 橫出 正之
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋、愛知
    • Year and Date
      2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] EP4受容体細胞内結合分子EPRAPはPP2Aにより脱リン酸化されることで抗炎症作用を示す2015

    • Author(s)
      藤川 理沙子, 樋口 聖, 南 学, 安井美加, 池堂太一, 永田学, 橫出 正之
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋、愛知
    • Year and Date
      2015-03-18
    • Related Report
      2014 Research-status Report
  • [Presentation] EP4 receptor-associated protein (EPRAP) in microglia promotes inflammation in the brain.2014

    • Author(s)
      Fujikawa, R., M. Minami, S. Higuchi, M. Yasui, T. Ikedo, M. Nagata, M. Yokode
    • Organizer
      Neuroscience2014 (Annual Meeting of Society for Neuroscience)
    • Place of Presentation
      Washington, DC, USA
    • Year and Date
      2014-11-18
    • Related Report
      2014 Research-status Report
  • [Presentation] EP4 receptor regulates obesity-related Inflammation and insulin sensitivity.2014

    • Author(s)
      Yasui, M., M. Minami, M. Yokode
    • Organizer
      The 9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress (MSDA 2014)
    • Place of Presentation
      Kyoto, Kyoto, Japan
    • Year and Date
      2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] EPRAP欠損マウスは注意欠陥・多動性症候群様の行動異常を示す2014

    • Author(s)
      藤川理沙子, 南 学, 樋口 聖, 横出 正之
    • Organizer
      第16回ブレインサイエンス研究会
    • Place of Presentation
      沖縄、沖縄
    • Year and Date
      2014-06-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of EP4 signaling in obesity-related inflammation.2014

    • Author(s)
      Yasui, M., M. Minami, M. Yokode
    • Organizer
      The 18th International Vascular Biology Meeting (IVBM2014)
    • Place of Presentation
      Kyoto, Kyoto, Japan
    • Year and Date
      2014-04-17
    • Related Report
      2014 Research-status Report
  • [Remarks]

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~rinsho/research/research_minami/

    • Related Report
      2015 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~rinsho/research/research_minami/

    • Related Report
      2014 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi