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Involvement of Cytoglobin expressed in hepatic stellate cells in the development of cancer derived from inflamed liver.

Research Project

Project/Area Number 25293177
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

KAWADA NORIFUMI  大阪市立大学, 大学院医学研究科, 教授 (30271191)

Co-Investigator(Kenkyū-buntansha) Le Thuy  大阪市立大学, 大学院医学研究科, 特任助教 (10572175)
Enomoto Masaru  大阪市立大学, 大学院医学研究科, 准教授 (20423874)
Tamori Akihiro  大阪市立大学, 大学院医学研究科, 准教授 (30291595)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords肝がん / サイトグロビン / 肝硬変 / 肝癌 / 線維芽細胞 / 動物モデル
Outline of Final Research Achievements

We have shown Cygb's anti-oxidative properties.Here,we clarified the role of Cygb in the development of liver fibrosis and cancer with different aetiologies.Model 1;25ppm DEN treatment for 25 weeks induced liver tumor formation in 100% of Cygb-/- mice compared to 44% in WT mice. Background liver developed fibrosis together with the augmented inflammatory reactions and oxidative stress conditions in Cygb-/- mice. Model 2;8-16 weeks of CDAA treatment provoked more steatohepatitis,fibrosis,and accumulated neutrophils in Cygb-/- mice than in WT.Interestingly,100% of Cygb-/- mice fed CDAA for 32 weeks developed liver cancer,while no tumor was found in WT.HSCs isolated from Cygb-/- mice exhibited the priming condition and the senescence-like phenotype with upregulated chemokine and cytokine mRNA expression and superoxide production.Thus,Cygb deficiency detetiorated liver fibrosis and cancer development caused by different etiologies,indicating the protective role of Cygb in organ insult.

Report

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

    (11 results)

All 2016 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Pathophysiological role of cytoglobin, the fourth globin in mammals, in liver diseases.2016

    • Author(s)
      Thuy Le TT, Hai NT, Hai H, Kawada N.
    • Journal Title

      Histol Histopathol.

      Volume: 31 Pages: 257-267

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Cytoglobin as a Marker of Hepatic Stellate Cell-derived Myofibroblasts.2015

    • Author(s)
      Kawada N.
    • Journal Title

      Front Physiol.

      Volume: 6 Pages: 329-329

    • DOI

      10.3389/fphys.2015.00329

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Cytoglobin Deficiency Promotes Liver Cancer Development from Hepatosteatosis through Activation of the Oxidative Stress Pathway.2015

    • Author(s)
      Thuy le TT, Matsumoto Y, Thuy TT, Hai H, Suoh M, Urahara Y, Motoyama H, Fujii H, Tamori A, Kubo S, Takemura S, Morita T, Yoshizato K, Kawada N
    • Journal Title

      The American Journal of Pathology

      Volume: 185 Issue: 4 Pages: 1045-1060

    • DOI

      10.1016/j.ajpath.2014.12.017

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of hepatic stellate cell cytoglobin in acute hepatocyte damage through the regulation of CYP2E1-mediated xenobiotic metabolism2015

    • Author(s)
      Yuga Teranishi, Tsutomu Matsubara, Kristopher W Krausz, Thi T T Le, Frank J Gonzalez, Katsutoshi Yoshizato,Kazuo Ikeda and Norifumi Kawada
    • Journal Title

      Laboratory Investigation

      Volume: 00 Pages: 1-10

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Cytoglobin Deficiency Promotes Liver Cancer Development from Hepatosteatosis through Activation of the Oxidative Stress Pathway2015

    • Author(s)
      Thuy le TT, Matsumoto Y, Thuy TT, Hai H, Suoh M, Urahara Y, Motoyama H, Fujii H, Tamori A, Kubo S, Takemura S, Morita T, Yoshizato K, Kawada N.
    • Journal Title

      Am J Pathol.

      Volume: 185 Pages: 1045-1060

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.2014

    • Author(s)
      Motoyama H, Komiya T, Thuy le TT, Tamori A, Enomoto M, Morikawa H, Iwai S,Uchida-Kobayashi S, Fujii H, Hagihara A, Kawamura E, Murakami Y, Yoshizato K,Kawada N.
    • Journal Title

      Lab Invest.

      Volume: 94 Pages: 192-207

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
  • [Presentation] Loss of Cytoglobin Exacerbates Liver Fibrosis and Cancer Development in Steatohepatitis by Activating the Oxidative Stress Pathway2015

    • Author(s)
      Le, Thuy T、Matsumoto, Yoshinari、Tuong Thi Van Thuy、Hoang Hai、Yoshizato, Katsutoshi、Kawada, Norifumi
    • Organizer
      American Association for the Study of Liver Diseases
    • Place of Presentation
      San Francisco(U S A)
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evolution of hepatic fibrosis reserch2015

    • Author(s)
      Kawada N
    • Organizer
      Asian Pacific Association for the Study of the Liver
    • Place of Presentation
      Istanbul (Turkey)
    • Year and Date
      2015-03-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 大阪市立大学大学院医学研究科肝胆膵病態内科学 医局ホームページ

    • URL

      http://www.med.osaka-cu.ac.jp/liver/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 大阪市立大学大学院医学研究科肝胆膵病態内科学医局ホームページ

    • URL

      http://www.med.osaka-cu.ac.jp/liver/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 大阪市立大学大学院医学研究科肝胆膵病態内科学医局ホームページ

    • URL

      http://www.med.osaka-cu.ac.jp/liver/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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