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Functional analysis of stap, a novel gene expressed in hepatic stellate cells and fibrotic liver tissue and its significance in clinicopathophysiology

Research Project

Project/Area Number 14570497
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 Shool of Medicine, Department of Hepatology, Assistant Professor of Medicine, 大学院・医学研究科, 講師 (30271191)

Co-Investigator(Kenkyū-buntansha) IKEDA Kazuo  Osaka City University, Graduate School of Medicine, Department of Anatomy, Associate Professor of Medicine, 大学院・医学研究科, 講師 (80275247)
SEKI Shuichi  Osaka City University, Graduate School of Medicine, Department of Hepatology, Associate Professor of Medicine, 大学院・医学研究科, 助教授 (50145778)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsstap / stellate cell / heme protein / globin / liver fibrosis / 肝星細胞 / 肝線維化 / STAP / グロビン / ヘム蛋白
Research Abstract

STAP consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cells. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin/STAP is. ubiquitously expressed in several organs although its deteiled localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin/STAP 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/STAP 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/STAP expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin/STAP is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Nakatani K, Okuyama H, et al.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis."Lab Invest.. 84. 91-101 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uyama N, Shimahara Y, et al.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture."J Hepatol.. 39. 749-755 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inagaki Y, Nemoto T, et al.: "Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice."Hepatology. 38. 890-899 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawai H, Kawada N, et al.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans."Biochemistry. 42. 5133-5142 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda N, Kawada N, et al.: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways."J Biol Chem.. 278. 18938-18944 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asahina K, Kawada N, et al.: "Characterization of human stellate cell activation-associated protein and its expression in human liver."Biochim Biophys Acta.. 1577. 471-475 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asahina K, Kawada N, Kristensen DB, Nakatani K, Seki S, Shiokawa M, Tateno C, Obara M, Yoshizato K.: "Characterization of Human stellate cell activation-associated protein and its expression in human liver"Biochim Biophys Acta. 1577(3). 471-475 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takashima T, Kawada N, Maeda N, Okuyama H, Uyama N, Seki S, Arakawa T.: "Pepstatin A attenuates the inhibitory effect of N-acetyl-L-cysteine on proliferation of hepatic myofibroblasts (stellate cells)"Eur J Pharmacol. 451(3). 265-270 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, Suzuki Y, Kojima S.: "Impaired liver regeneration in mice by lipopolysaccharide via TNF-alpha/kallikrein-mediated activation of latent TGF-beta"Gastroenterology. 1223(1). 352-364 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seki S, Kitada T, Kawada N, Kadoya H, Sakaguchi H, Nakatani K, Satake K.: "Fatty change in human hepatocellular carcinoma cell lines derived from patients with antibodies to hepatitis C virus"Hepatogastroenterology. 49(44). 340-344 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uyama N, Shimahara Y, Kawada N, Seki S, Okuyama H, Iimuro Y, Yamaoka Y.: "Regulation of cultured rat hepatocyte proliferation by stellate cells"J Hepatol. 36(5). 590-599 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okuyama H, Shimahara Y, Kawada N.: "The hepatic stellate cell in the post-genomic era"Histol Histopathol. 17(2). 487-495 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakatani K, Seki S, Kawada N, Kitada T, Yamada T, Sakaguchi H, Kadoya H, Ikeda K, Kaneda K.: "Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis"Virchows Arch. 441(5). 466-474 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seki S, Kitada T, sakaguchi H, Iwai S, Kawada N, Hayashi Y, Kim SR: "Expression of progenitor cell markers in livers with fulminant massive necrosis"Hepatol Res. 25(2). 149-157 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans"Biochemistry. 42(17). 5133-5142 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okuyama H, Nakamura H, Shimahara Y, Araya S, Kawada N, Yamaoka Y, Yodoi J.: "Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice"Hepatology. 37(5). 353-364 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kobayashi S, Seki S, Kawada N, Morikawa H, Nakatani K, Uyama N, Ikeda K, Nakajima Y, Arakawa T, Kaneda K.: "Apoptosis of T cells in the hepatic fibrotic tissue of the rat: a possible inducing role of hepatic myofibroblast-like cells"Cell Tissue Res. 311(3). 353-364 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda N, Kawada N, Seki S, Arakawa T, Ikeda K, Iwao H, Okuyama H, Hirabayashi J, Kasai K, Yoshizato K: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways"J Biol Chem. 278(21). 18938-18944 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seki s, Kitada T, Iwai S, Kadoya H, Yamada T, Kawada N, Sakaguchi H, Wakasa K: "Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune hepatitis"Hepatogastroenterology. 50(53). 1274-1277 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uyama N, shimahara Y, Okuyama H, kawada N, Kamo S, Ikeda K, Yamaoka Y.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture"J Hepatol. 39(5). 749-755 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inagaki Y, Nemoto T, Kushida M, Sheng Y, Higashi K, Ikeda K, Kawada N, Shirasaki F, Takehara K, Sugiyama K, fujii M, Yamauchi H, Nakao A, de Crombrugghe B, Watanabe T, Okazaki I.: "Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice"Hepatology. 38(4). 890-899 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imanishi Y, Maeda N, Matsui H, Takashima T, Seki S, Arakawa T, Kawada N.: "Suppression of Rat Stellate Cell Activation and Liver Fibrosis by a Japanese Herbal Medicine, Inchinko-to (TJ135)"Comp Hepatol. 3 Suppl 1. S11 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda N, Kawada N, Seki S, Ikeda K, Okuyama H, Hirabayashi J, Kasai KI, Yoshizato K.: "Involvement of Galectin-1 and Galectin-3 in Proliferation and Migration of Rat Hepatic Stellate Cells in Culture"Comp Hepatol. 3 Suppl 1. S10 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui H, Takashima T, Maeda N, Imanishi Y, Uyama N, Okuyama H, Kawada N.: "Amino acids, L-Cysteine and L-Methionine, Attenuate Activation of Rat Stellate Cells in Primary Culture"Comp Hepatol. 3 Suppl 1. S9 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okuyama H, shimahara Y, Nakamura H, Araya S, Kawada N, Yamaoka Y, Yodoi J.: "Thioredoxin prevents thioacetamide-induced acute hepatitis"Comp Hepatol. 3 Suppl 1. S6 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawada N.: "Molecular mechanism of stellate cell activation and therapeutic strategy for liver fibrosis"Comp Hepatol (No abstract available). 3 Suppl 1. S3 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim DH, Nakajima Y, Seki S, Kawada N, Yoshizato K.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis"Lab Invest. 84(1). 91-101 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakatani K, Okuyama H, et al.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis."Lab Invest.. 84. 91-101 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Uyama N, Shimahara Y, et al.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture."J Hepatol.. 39. 749-755 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inagaki Y, Nemoto T, et al.: "Interferon alfa down-regulates collagen gene transcription and suppresses experimantal hepatic fibrosis in mice."Hepatology. 38. 890-899 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawai H, Kawada N, et al.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans."Biochemistry. 42. 5133-5142 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maeda N, Kawada N, et al.: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways."J Biol Chem.. 278. 18938-18944 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Asahina K, Kawada N, et al.: "Characterization of human stellate cell activation-associated protein and its expression in human liver."Biochim Biophys Acta.. 1577. 471-475 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akita K, Okuno M, Enya M, et al.: "Impaired liver regeneration in mice by lipopolysaccharide via TNF-α/kallikrein-mediated activation of latent TGFβ"Gastroenterology. 123. 352-364 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uyama N, Kawada N, Okuyama H, et al.: "Regulation of hepatocyte proliferation by stellate cell"J. Hepatol.. 36. 590-599 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakatani K, Seki S, Kawada N, et al.: "Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis"Virchows Archiv. 441. 466-474 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashima T, Kawada N, Maeda N, et al.: "Pepstatin A attenuates the inhibitory effect of N-acetyl-cysteine on proliferation of hepatic myofibroblasts (stellate cells)"Eur. J. Pharmacol.. 451. 265-270 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asahina K, Kawada N, Kristensen DB, et al.: "Characterization of Human stellate cell activation-associated protein (STAP) and its expression in human liver"Biochim Biophys Acta. 1577. 471-475 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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