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Molecular mechanism of tissue fibrosis and develpment of revolutionary anti-fibrotic therapy

Research Project

Project/Area Number 25670439
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Endocrinology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OGAWA Yoshihiro  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (70291424)

Co-Investigator(Kenkyū-buntansha) YAMASAKI Sho  九州大学, 生体防御医学研究所, 教授 (40312946)
Co-Investigator(Renkei-kenkyūsha) TANAKA Miyako  東京医科歯科大学, 大学院医歯(薬)学総合研究科, メディカルフェロー (60622793)
Project Period (FY) 2013-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords線維化 / マクロファージ / Mincle / 脂肪組織 / 線維芽細胞 / crown-like structure / 肥満 / 細胞死
Research Abstract

Fibrosis is a final, common pathological outcome of a variety of chronic inflammatory diseases. In this study, we focused on Macrophage-inducible C-type lectin (Mincle), a pathogen sensor that recognizes Mycobacterium tuberculosis and is induced in obese adipose tissue and investigated the role of Mincle in the regulation of adipose tissue fibrosis. In the obese adipose tissue, Mincle was expressed mainly in proinflammatory M1 macrophages. Mincle stimulation caused the upregulation of genes related to fibrogenesis in peritoneal macrophages. Furthermore, Mincle stimulation by trehalose 6,6'-dimycolate, an exogenous ligand for Mincle, in adipose tissue resulted in adipose tissue fibrosis. These observations suggest that Mincle activation in obese adipose tissue leads to the progression of adipose tissue fibrosis, thereby suggesting that Mincle antagonism offers an novel anti-fibrotic therapy for chronic fibrotic diseases.

Report

(2 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (23 results)

All 2014 2013 Other

All Journal Article (13 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 3 results) Remarks (2 results)

  • [Journal Article] PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.2014

    • Author(s)
      Y. Hatazawa, M. Tadaishi, Y. Nagaike, A. Morita, Y. Ogawa, O. Ezaki, T. Takai-Igarashi, Y. Kitaura, Y. Shimomura, Y. Kamei*, S. Miura*
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 3 Pages: e91006-e91006

    • DOI

      10.1371/journal.pone.0091006

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible involvement of Opa-interacting protein 5 in adipose proinflammation and obesity.2014

    • Author(s)
      Inoue K, Maeda N, Mori T, Sekimoto R, Tsushima Y, Matsuda K, Yamaoka M, Suganami T, Nishizawa H, Ogawa Y, Funahashi T, Shimomura I.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 2 Pages: e87661-e87661

    • DOI

      10.1371/journal.pone.0087661

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Endothelial PGC-1α mediates vascular dysfunction in diabetes2014

    • Author(s)
      N. Sawada, A. Jiang, F. Takizawa, A. Safdar, A. Manika, Y. Tesmenitsky, K.-T. Kang, J. Bischoff, H. Kalwa, J.L. Sartoretto, Y. Kamei, L.E. Benjamin, H. Watada, Y. Ogawa, Y. Higashikuni, C.W. Kessinger, F.A. Jaffer, T. Michel, M. Sata, K. Croce, R. Tanaka, Z Arany
    • Journal Title

      Cell Metab

      Volume: 19 Issue: 2 Pages: 246-58

    • DOI

      10.1016/j.cmet.2013.12.014

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paternal allele influences high fat diet-induced obesity.2014

    • Author(s)
      S. Morita, T. Horii, M. Kimura, Y. Arai, Y. Kamei, Y. Ogawa, I. Hatada.
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 1 Pages: e85477-e85477

    • DOI

      10.1371/journal.pone.0085477

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular complications and coagulation-related changes in the perioperative period in Japanese patients undergoing non-cardiac surgery2014

    • Author(s)
      Aoyama-Mani C, Kawachi S, Ogawa Y, Kato N.
    • Journal Title

      J. Atheroscler. Thromb.

      Volume: 21(5) Pages: 414-34

    • NAID

      130004444736

    • Related Report
      2013 Final Research Report
  • [Journal Article] An increase in the EPA/AA ratio is associated with improved arterial stiffness in obese patients with Dyslipidemia2014

    • Author(s)
      Ito R, Satoh-Asahara N, Yamakage H, Sasaki Y, Odori S, Kono S, Wada H, Suganami T, Ogawa Y, Hasegawa K, Shimatsu A.
    • Journal Title

      J. Atheroscler. Thromb.

      Volume: 21(3) Pages: 248-60

    • NAID

      130004444714

    • Related Report
      2013 Final Research Report
  • [Journal Article] Activating transcription factor 4 links metabolic stress to interleukin-6 expression in macrophages.2014

    • Author(s)
      Iwasaki Y, Suganami T, Hachiya R, Shirakawa I, Kim-Saijo M, Tanaka M, Hamaguchi M, Takai-Igarashi T, Nakai M, Miyamoto Y, Ogawa Y.
    • Journal Title

      Diabetes

      Volume: 63 Issue: 1 Pages: 152-61

    • DOI

      10.2337/db13-0757

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic crown-like structure : a unique histological feature in non-alcoholic steatohepatitis in mice and humans2013

    • Author(s)
      M. Itoh, H. Kato, T. Suganami, K. Konuma, Y. Marumoto, S. Terai, H. Sakugawa, S. Kanai, M. Hamaguchi, T. Fukaishi, S. Aoe, K. Akiyoshi, Y. Komohara, M. Takeya, I. Sakaida, Y. Ogawa
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 12 Pages: e82163-e82163

    • DOI

      10.1371/journal.pone.0082163

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel role for adipose ephrin-B1 in inflammatory response2013

    • Author(s)
      Mori T, Maeda N, Inoue K, Sekimoto R, Tsushima Y, Matsuda K, Yamaoka M, Suganami T, Nishizawa H, Ogawa Y, Funahashi T, Shimomura I
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 10 Pages: e76199-e76199

    • DOI

      10.1371/journal.pone.0076199

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of chronic inflammation in adipose tissue in the pathophysiology of obesity.2013

    • Author(s)
      Suganami T, Ogawa Y.
    • Journal Title

      Nihon Rinsho

      Volume: 71(2) Pages: 225-30

    • NAID

      40019565209

    • Related Report
      2013 Final Research Report
  • [Journal Article] Analysis of DNA methylation change induced by Dnmt3b in mouse hepatocytes2013

    • Author(s)
      Takahashi M, Kamei Y, Ehara T, Yuan X, Suganami T, Takai-Igarashi T, Hatada I, Ogawa Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 434 Issue: 4 Pages: 873-878

    • DOI

      10.1016/j.bbrc.2013.04.041

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero2013

    • Author(s)
      Y.K. Kohmura, N. Kanayama, K. Muramatsu, N. Tamura, C. Yaguchi, T. Uchida, K. Suzuki, K. Sugihara, S. Aoe, T. Sasaki, T. Suganami, Y. Ogawa, H. Itoh
    • Journal Title

      Reprod. Sci.

      Volume: 20 Issue: 7 Pages: 813-827

    • DOI

      10.1177/1933719112466300

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 脂肪組織・異所性脂肪蓄積と老化関連疾患2013

    • Author(s)
      土屋恭一郎、菅波孝祥、小川佳宏
    • Journal Title

      実験医学増刊

      Volume: 30 Pages: 3274-3280

    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of parenchymal-stromal cell interaction in metabolic diseases.2014

    • Author(s)
      Ogawa Y.
    • Organizer
      2014 Keystone Symposia on Molecular and Cellular Biology:
    • Place of Presentation
      Innate Immunity, Metabolism and Vascular Injury Whistler, Canada
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of metabolic genes by DNA methylation. 8th World Congress on Developmental Origins of Health and Disease.2013

    • Author(s)
      Ogawa Y.
    • Organizer
      SUTEC
    • Place of Presentation
      Singapore
    • Related Report
      2013 Final Research Report
  • [Presentation] Chronic inflammation and ectopic fat accumulation in the metabolic syndrome.2013

    • Author(s)
      Ogawa Y.
    • Organizer
      2013 International Conference on Diabetes and Metabolism (ICDM2013) & 5th Scientific Meeting of the Asian Association for the Study of Diabetes (5th AASD Scientific Meeting)
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] ATF4 Plays Critical Roles in Saturated Fatty Acid induced Il-6 Expression in Macropheges2013

    • Author(s)
      Iwasaki Y, Suganami T, Hachiya R, Shirakawa I, Hamaguchi M, Ogawa Y
    • Organizer
      The Endocrine Society's 95th Annual Meeting & Expo
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 慢性炎症と異所性脂肪蓄積2013

    • Author(s)
      小川佳宏
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本、日本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 生活習慣病の基盤病態としての慢性炎症2013

    • Author(s)
      小川佳宏
    • Organizer
      第28回日本糖尿病合併症学会
    • Place of Presentation
      旭川、日本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 生活習慣病の基盤病態としての慢性炎症2013

    • Author(s)
      小川佳宏
    • Organizer
      第47回日本小児内分泌学会学術集会
    • Place of Presentation
      東京、日本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 脂肪組織炎症における病原体センサー・Mincleの意義2013

    • Author(s)
      田中 都、菅波孝祥、池田賢司、小宮 力、白川伊吹、越智 梢、青江誠一郎、小川佳宏
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京、日本
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 東京医科歯科大学大学院医歯学総合研究科分子内分泌代謝学分野

    • URL

      http://www.tmd.ac.jp/grad/cme/index.html

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2016-11-25  

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