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Functional analysis of cytoglobin that is expressed and induced in liver cirrhosis

Research Project

Project/Area Number 16590618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

KAWADA Norifumi  Osaka City University, Graduate School of Medicine, Department of Hepatology, Associate Professor, 大学院・医学研究科, 助教授 (30271191)

Co-Investigator(Kenkyū-buntansha) IKEDA Kazuo  Osaka City University, Graduate School of Medicine, Department of Anatomy, Associate Professor, 大学院・医学研究科, 助教授 (80275247)
NAKATANI Kazuki  Osaka City University, Graduate School of Medicine, Department of Anatomy, Lecturer, 大学院・医学研究科, 講師 (60295699)
YOSHIZATO Katsutoshi  Hiroshima University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (20095516)
OBARA Masanobu  Hiroshima University, Graduate School of Science, Associate Professor, 大学院・理学研究科, 助教授 (60132479)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsstellate cell / liver fibrosis / globin / heme / oxygen / myofibroblast / vitamin A / 抗ペプチド
Research Abstract

Cytoglobin consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cell, an unique fibroblastic cell in the liver. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin is ubiquitously expressed in several organs including the liver, pancreas, kidney, spleen, intestine and lung, although its detailed localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin is uniquely localized in fibroblast-like cells in splanchnic organs, namely vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. Expression of cytoglobin was upregulated in fibrotic lesions of pancreas and kidney in which activated fibroblast-like cells or myofibroblasts increased in number. In cultured hepatic stellate cells, cytoglobin expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder. Additional experiments obtained by purified and crystallized cytoglobin revealed that this protein bind oxygen, nitric oxide and carbon monoxide in a manner similar to myoglobin. Thus, cytoglobin is a novel globin that play a role in oxygen transport in visceral myofibroblasts and in contrast myoglobin seems to be a muscle cell-specific oxygen carrier.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005 2004

All Journal Article (18 results)

  • [Journal Article] BMP-7 opposes TGF-beta1-mediated collagen induction in mouse pulmonary myofibroblasts through Id2.2006

    • Author(s)
      Izumi N, Mizuguchi S, et al.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol. 290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] BMP-7 opposes TGF-beta1-mediated collagen induction in mouse pulmonary myofibroblasts through Id2.2006

    • Author(s)
      Izumi N, Mizuguchi S, Inagaki Y, Saika S, Kawada N, Nakajima Y, Inoue K, Suehiro S, Friedman SL, Ikeda K.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol. 290(1)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of thioredoxin prevents thioacetarnide-induced hepatic fibrosis in mice.2005

    • Author(s)
      Okuyama H, Nakamura H, et al.
    • Journal Title

      J Hepatol. 42

      Pages: 117-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of S-adenosyl-L-methionine on the activation, proliferation and contraction of hepatic stellate cells.2005

    • Author(s)
      Matsui H, Kawada N
    • Journal Title

      Eur J Pharmacol. 509

      Pages: 31-36

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Cell type-specific intervention of transforming growth factor beta/Smad signaling suppresses collagen gene expression and hepatic fibrosis in mice.2005

    • Author(s)
      Inagaki Y, Kushida M, et al.
    • Journal Title

      Gastroenterology 129

      Pages: 259-268

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Analysis of proteins dominantly expressed in hepatic stellate cells of activated phenotype.2005

    • Author(s)
      Kawada N
    • Journal Title

      Methods Mol Med. 117

      Pages: 371-379

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin.2005

    • Author(s)
      Sawai H, Makino M, et al.
    • Journal Title

      Biochemistry 44

      Pages: 13257-13265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice.2005

    • Author(s)
      Okuyama H, Nakamura H, Shimahara Y, Uyama N, Kwon YW, Kawada N, Yamaoka Y, Yodoi J.
    • Journal Title

      J Hepatol. 42(1)

      Pages: 117-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of S-adenosyl-L-methionine on the activation, proliferation and contraction of hepatic stellate cells.2005

    • Author(s)
      Matsui H, Kawada N.
    • Journal Title

      Eur J Pharmacol. 509(1)

      Pages: 31-36

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell type-specific intervention of transforming growth factor beta/Smad signaling suppresses collagen gene expression and hepatic fibrosis in mice.2005

    • Author(s)
      Inagaki Y, Kushida M, Higashi K, Itoh J, Higashiyama R, Hong YY, Kawada N, Namikawa K, Kiyama H, Bou-Gharios G, Watanabe T, Okazaki I, Ikeda K.
    • Journal Title

      Gastroenterology. 129(1)

      Pages: 259-268

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of proteins dominantly expressed in hepatic stellate cells of activated phenotype.2005

    • Author(s)
      Kawada N.
    • Journal Title

      Methods Mol Med. 117

      Pages: 371-379

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin.2005

    • Author(s)
      Sawai H, Makino M, Mizutani Y, Ohta T, Sugimoto H, Uno T, Kawada N, Yoshizato K, Kitagawa T, Shirro Y
    • Journal Title

      Biochemistry. 44(40)

      Pages: 13257-13265

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice.2005

    • Author(s)
      Okuyama H, Nakamura H, et al.
    • Journal Title

      J Hepatol. 42

      Pages: 117-123

    • Related Report
      2005 Annual Research Report 2004 Annual Research Report
  • [Journal Article] Effect of S-adenosyl-L-methionine on the activation, proliferation and contraction of hepatic stellate cells.2005

    • Author(s)
      Matsui H, Kawada N.
    • Journal Title

      Eur J Pharmacol. 509

      Pages: 31-36

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis.2004

    • Author(s)
      Nakatani K, Okuyama H, et al.
    • Journal Title

      Lab Invest. 84

      Pages: 91-101

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Herb medicine Inchin-ko-to(TJ-135) regulates PDGF-BB-dependent signaling pathways of hepatic stellate cells in primary culture and attenuates development of liver fibrosis induced by thioacetamide administration in rats.2004

    • Author(s)
      Imanishi Y, Maeda N, et al.
    • Journal Title

      J Hepatol. 41

      Pages: 242-250

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Typing of hepatic nonparenchymal cells using fibulin-2 and cytoglobin/STAP as liver fibrogenesis-related markers.2004

    • Author(s)
      Tateaki Y, Ogawa T, et al.
    • Journal Title

      Histochem Cell Biol. 122

      Pages: 41-49

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Structural basis of human cytoglobin for ligand binding.2004

    • Author(s)
      Sugimoto H, Makino M, et al.
    • Journal Title

      J Mol Biol. 339

      Pages: 873-885

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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