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Role of EP4 receptor-associated protein in regulating macrophage activation

Research Project

Project/Area Number 23590361
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionKyoto University

Principal Investigator

MINAMI Manabu  京都大学, 医学(系)研究科(研究院), 助教 (90511907)

Co-Investigator(Renkei-kenkyūsha) SENO Hiroshi  京都大学, 大学院医学研究科, 講師 (90335266)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords分子病態学 / マクロファージ / 慢性炎症 / 細胞内シグナル伝達 / シグナル伝達
Research Abstract

In this study we aimed to dissect the significance and pathophysiological roles of EP4 receptor-associated protein, EPRAP, a novel cytoplasmic regulator of macrophage activation. We generated EPRAP-deficient mice as well as transgenic mice with enforced expression of EPRAP specifically in macrophages. We used these mice and created animal models of human inflammatory bowel diseases and pulmonary fibrosis. In both experiments, EPRAP deficiency markedly increased infiltrated macrophage activation and local inflammation, resulting in significant decrease in survival rates. In addition, we figured out that EPRPA mitigated the MEK-ERK pathway activation and inhibited macrophage activation in the inflamed lesions. Our results indicated that EPRAP plays crucial roles in the pathogenesis and outcome of various inflammatory diseases by regulating macrophage activation in vivo.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (39 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 11 results) Presentation (13 results) Book (9 results) Remarks (2 results)

  • [Journal Article] Dclk1 distinguishes between tumor and normal stem cells in the intestine.2013

    • Author(s)
      Yuki Nakanishi, et. al.
    • Journal Title

      Nature Genetics

      Volume: 45 Issue: 1 Pages: 98-103

    • DOI

      10.1038/ng.2481

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Role of Gas6 in Intestinal Tumorigenesis.2013

    • Author(s)
      Yuki Nakanishi, et. al.
    • Journal Title

      Carcinogenesis

      Volume: (印刷中) Issue: 7 Pages: 1567-1574

    • DOI

      10.1093/carcin/bgt069

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An international survey of physicians regarding clinical trials: a comparison between Kyoto University Hospital and Seoul National University Hospital.2013

    • Author(s)
      Ito-Ihara T, Hong JH, Kim OJ, Sumi E, Kim SY, Tanaka S, Narita K, Hatta T, Choi EK, Choi KJ, Miyagawa T, Minami M, Murayama T, Yokode M.
    • Journal Title

      BMC Med Res Methodol.

      Volume: 13 Issue: 1 Pages: 130-130

    • DOI

      10.1186/1471-2288-13-130

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 動脈硬化性疾患予防ガイドライン2012 Update「家族歴」2013

    • Author(s)
      南 学
    • Journal Title

      動脈硬化予防

      Volume: 11 Pages: 119-120

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 動脈硬化性疾患の包括的管理2013

    • Author(s)
      南 学、横出 正之
    • Journal Title

      The Lipid

      Volume: 24 Pages: 42-47

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 動脈硬化予防における多面的アプローチ2013

    • Author(s)
      南 学
    • Journal Title

      日本臨床 増刊号

      Volume: 71 Pages: 36-40

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Ezetimibe Ameliorates Early Diabetic Nephropathy in db/db Mice2012

    • Author(s)
      Tamura, Y., T. Murayama, M. Minami, T. Matsubara, M. Yokode, H. Arai
    • Journal Title

      J Atheroscler Thromb

      Volume: 19 (7)(PMID: 22498767) Pages: 608-618

    • NAID

      130004444694

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ezetimibe Ameliorates Early Diabetic Nephropathy in db/db Mice2012

    • Author(s)
      Tamura, Y., T. Murayama, M. Minami, T. Matsubara, M. Yokode, and H. Arai.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 19 Issue: 7 Pages: 608-618

    • DOI

      10.5551/jat.11312

    • NAID

      130004444616

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 肥満・動脈硬化の発症における新規マクロファージ活性化調節因子EPRAP/Fem1aの機能解析2012

    • Author(s)
      南 学
    • Journal Title

      Therapeutic Research

      Volume: 33 Pages: 821-823

    • Related Report
      2012 Research-status Report
  • [Journal Article] SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation2011

    • Author(s)
      Uza N, Nakase H, Yamamoto S, Yoshino T, Takeda Y, Ueno S, Inoue S, Mikami S, Matsuura M, Shimaoka T, Kume N, Minami M, Yonehara S, Ikeuchi H, Chiba T
    • Journal Title

      Gut

      Volume: 60 Issue: 11 Pages: 1494-1505

    • DOI

      10.1136/gut.2010.221879

    • NAID

      120003497105

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] COX-2 inhibition alters the phenotype of tumor associated macrophages from M2 to M1 in ApcMin/+ mouse polyps2011

    • Author(s)
      Nakanishi Y, Seno H, Kawada M, et al
    • Journal Title

      Carcinogenesis

      Volume: 32(9) Issue: 9 Pages: 1333-1339

    • DOI

      10.1093/carcin/bgr128

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential effect of statins on diabetic nephropathy in db/db mice2011

    • Author(s)
      Tamura Y, Murayama T, Minami M, Yokode M, Arai H.
    • Journal Title

      Int J Mol Med

      Volume: 28 Pages: 683-687

    • DOI

      10.3892/ijmm.2011.769

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation.2011

    • Author(s)
      Uza, N, H. Nakase, S. Yamamoto, T. Yoshino, Y. Takeda, S. Ueno, S. Inoue, S. Mikami, M. Matsuura, T. Shimaoka, N. Kume, M. Minami, S. Yonehara, H. Ikeuchi, T. Chiba.
    • Journal Title

      Gut

      Volume: 60 Pages: 1494-505

    • NAID

      120003497105

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps.2011

    • Author(s)
      Nakanishi, Y., M. Nakatsuji, H. Seno, S. Ishizu, R. Akitake-Kawano, K. Kanda, T. Ueo, H. Komekado, M. Kawada, M. Minami, T. Chiba.
    • Journal Title

      Carcinogenesis

      Volume: 32 Pages: 1333-9

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential effect of statins on diabetic nephropathy in db/db mice.2011

    • Author(s)
      Tamura, Y., T. Murayama, M. Minami, M. Yokode, H. Arai.
    • Journal Title

      Int J Mol Med

      Volume: 28 Pages: 683-7

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] EP4 receptor associated protein (EPRAP) in macrophages protects against bleomycin induced pulmonary inflammation in mice2014

    • Author(s)
      樋口聖, 南学, 中辻正人, 藤川理沙子, 安井美加, 村山敏典, 橫出正之
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台(Oral presentation)
    • Year and Date
      2014-03-19
    • Related Report
      2013 Final Research Report
  • [Presentation] EP4 receptor associated protein (EPRAP) in microglia promotes inflammation in the central nervous system2014

    • Author(s)
      藤川理沙子, 南学, 樋口聖, 安井美加, 池堂太一, 永田学, 橫出正之
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台(Oral presentation)
    • Year and Date
      2014-03-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of EP4 signaling in obesity-related inflammation–肥満に伴う慢性炎症におけるEP4受容体の機能解析–2013

    • Author(s)
      Yasui, M., M. Minami, M. Yokode.
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸(Poster presentation)
    • Year and Date
      2013-12-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of EP4-EPRAP signaling in obesity and diabetes–肥満や2型糖尿病におけるEP4受容体およびEPRAPの機能解析–2013

    • Author(s)
      安井美加, 南学, 樋口聖, 橫出正之
    • Organizer
      第45回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京(Poster presentation)
    • Year and Date
      2013-07-19
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of EP4 receptor associated protein in brain2013

    • Author(s)
      Fujikawa R., M. Minami, S. Higuchi, M. Yasui, M. Yokode
    • Organizer
      第15回ブレインサイエンス研究会
    • Place of Presentation
      博多(福岡)(Oral presentation)
    • Year and Date
      2013-06-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of EP4-EPRAP signaling in obesity and diabetes2013

    • Author(s)
      Yasui, M., M. Minami, M. Yokode
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      博多(福岡)(Oral presentation)
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] がん化学療法の進歩と心血管合併症-分子標的治療時代の循環器マネージメントのあり方-2013

    • Author(s)
      南学
    • Organizer
      第77回日本循環器学会
    • Place of Presentation
      横浜(モーニングレクチャー)
    • Year and Date
      2013-03-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of bioactive eicosanoid signaling in atherosclerosis and insulin resistance2011

    • Author(s)
      Minami, M., M. Yokode
    • Organizer
      第19回日本血管生物医学会
    • Place of Presentation
      東京(シンポジウム指定講演)
    • Year and Date
      2011-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of bioactive eicosanoid signaling in atherosclerosis and insulin resistance.2011

    • Author(s)
      南 学
    • Organizer
      第19回日本血管生物医学会
    • Place of Presentation
      東京ステーションコンファレンス(東京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] Role of EP4-EPRAP signaling in obesity and diabetes–肥満や2型糖尿病におけるEP4 受容体およびEPRAP の機能解析–

    • Author(s)
      安井 美加, 南 学, 樋口 聖, 橫出 正之
    • Organizer
      第45回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of EP4 signaling in obesity-related inflammation –肥満に伴う慢性炎症におけるEP4 受容体の機能解析–

    • Author(s)
      Yasui, M., M. Minami, M. Yokode
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] EP4 receptor–associated protein (EPRAP) in macrophages protects against bleomycin–induced pulmonary inflammation in mice.

    • Author(s)
      樋口 聖, 南 学, 中辻 正人, 藤川 理沙子, 安井 美加, 村山 敏典, 橫出 正之
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Annual Research Report
  • [Presentation] EP4 receptor–associated protein (EPRAP) in microglia promotes inflammation in the central nervous system.

    • Author(s)
      藤川 理沙子, 南 学, 樋口 聖, 安井 美加, 池堂 太一, 永田 学, 橫出 正之
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Annual Research Report
  • [Book] 特集動脈硬化性疾患予防ガイドライン2012 Update, シリーズ危険因子「家族歴」動脈硬化予防(11 (4))2013

    • Author(s)
      南学
    • Related Report
      2013 Final Research Report
  • [Book] 特集動脈硬化性疾患予防ガイドライン2012, 4. 動脈硬化性疾患の包括的管理(24 (1))2013

    • Author(s)
      南学, 横出正之
    • Publisher
      The Lipid
    • Related Report
      2013 Final Research Report
  • [Book] 動脈硬化性疾患予防ガイドライン2012改訂のポイント前編(35(3))2013

    • Author(s)
      南学
    • Publisher
      都薬雑誌
    • Related Report
      2013 Final Research Report
  • [Book] 動脈硬化性疾患予防ガイドライン2012改訂のポイント後編(35(4)2013

    • Author(s)
      南学
    • Publisher
      都薬雑誌
    • Related Report
      2013 Final Research Report
  • [Book] 脂質異常症治療薬の特徴と薬剤使用に際しての留意点服薬指導へのアドバイス(35(5)2013

    • Author(s)
      南学
    • Publisher
      都薬雑誌
    • Related Report
      2013 Final Research Report
  • [Book] 特集脂質異常症—基礎・臨床研究の最新知見—, 動脈硬化予防における多面的アプローチ(増刊号 71 (3))2013

    • Author(s)
      南学
    • Publisher
      日本臨床
    • Related Report
      2013 Final Research Report
  • [Book] 増加する癌外来化学療法循環器系の副作用に注意を—(2013年6月号特別編集版)2013

    • Author(s)
      南学
    • Publisher
      日経メディカル
    • Related Report
      2013 Final Research Report
  • [Book] 肥満・動脈硬化の発症における新規マクロファージ活性化調節因子EPRAP/Fem1aの機能解析(33(6))2012

    • Author(s)
      南学
    • Publisher
      herapeutic Research
    • Related Report
      2013 Final Research Report
  • [Book] 高齢者における脂質管理・動脈硬化学会からのメッセージ(49 (10))2011

    • Author(s)
      南学, 横出正之
    • Publisher
      Geratric Med
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research 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
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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