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2002 Fiscal Year Final Research Report Summary

Development of high sensitive assay method to detect tissue specific regeneration markers -Protein chip -ELISA specific for liver regeneration

Research Project

Project/Area Number 12357017
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionMie University

Principal Investigator

SUZUKI Koji  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70077808)

Co-Investigator(Kenkyū-buntansha) IDO Masaru  Mie University Hospital, Associate Professor, 医学部附属病院, 助教授 (90167263)
KAMADA Haruhiko  Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (00324509)
HAYASHI Tatsuya  Mie University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00242959)
YAMAGISHI Toshiya  Mitsubishi Chemical Corporation, Research fellow, 横浜総合研究所, 研究職
NAKA Daichi  Mitsubishi Chemical Corporation, Research fellow, 横浜総合研究所, 研究職
Project Period (FY) 2000 – 2002
Keywordsliver regeneration / protein C inhibitor / Hepatocyte growth factor activator / hepatocyte growth factor / activated protein C / inflammation / protein chip-ELISA / molecular markers for tissue regeneration
Research Abstract

The serine protease hepatocyte growth factor activator (HGFA) is formed from its inactive precursor (proHGFA) by thrombin generated at sites of tissue injury. Recently, we found that protein C inhibitor (PCI), a plasma serine protease inhibitor of activated protein C, inhibits thrombin-catalyzed protein C activation in the presence of thrombomodulin. Here we studied whether thrombomodulin stimulates the thrombin-catalyzed proHGFA activation by PCI. we determined the active HGFA using chromogenic peptide substrate specific for HGFA and also by detection HGF precursor activation, that is proteolytically activated by HGFA, on SDS-PAGE.. We further determined HGFA-PCI complex formation by protein chip-ELISA. As results, we could not demonstrate PCI inhibition of thrombin-catalyzed proHGFA activation regardless of the presence or absence of thrombomodulin, but found that PCI directly inhibits activated HGFA by forming a complex with it. This PCI inhibition of HGFA resulted in HGFA-catalyzed activation of HGF precursor. The HGFA-PCI complex levels were increased in plasma of patients with either hepatitis or hepoatocellular carcinoma, who had been subjected to either medical or surgical treatments, and also in plasma of healthy donors participating in adult-to-adult living-donor liver transplantation. From these findings, we suggest that PCI may play a role as a potent regulator of activated HGFA, implying a role for it in the regulation of tissue repair including the liver regeneration.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Yuasa, H., Suzuki, K., et al.: "Bovine protein C inhibitor has a unique reactive site and can transiently inhibit plasmin."Thromb.Haemost.. 83. 262-267 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki, K., Hayashi, T.: "Cis-elements required for expression of human protein C inhibitor (PCI) gene in HepG2 cells and itsandrogen-dependent expression in rat reproductive organs."Sem.Thromb.Hemost.. 126. 75-84 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, R., Suzuki, K., et al.: "Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable state."Am.J.Hematol.. 65. 35-40 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki, K.: "Protein C inhibitor (PAI-3) : structure and multi-function."Fibrinol.Proteol.. 14. 133-145 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuneyoshi, N., Suzuki, K., et al.: "Expression and anticoagulant function of the endothelial cell protein C receptor EPCR in cancer cell lines."Thromb.Haemost.. 85. 356-361 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui, H., Suzuki, K., et al.: "Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse."Am.J.Respir.Crit.Care Med.. 163. 1660-1668 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu, S., Suzuki, K, et al.: "Activated protein C inhibits the expression of Platelet-derived growth factor in the lung."Am.J.Respir.Crit.Care Med.. 167. 1416-1426 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujimoto H., Suzuki, K, et al.: "Thrombin-activatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease."Am.J.Respir.Crit.Care Med.. 167. 1687-1694 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wakita, T., Suzuki, K., et al.: "Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma."Int.J.Cancer. 108. 516-523 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi, T., Suzuki, K., et al.: "Characterization of mice transgenic for a human protein C inhibitor gene, useful as in vivo models for the evaluation of the therapeutic effects of human activated protein C."J.Thromb.Haemost.. (In Press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki K., Gabazza, E.C., et al.: "Protective role of activated protein C in lung and airway remodeling."Crit.Care Med.. (In Press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishioka, J., Suzuki, K., et al.: "Protein C inhibitor potently inhibits activated hepatocyte growth factor activator : a possible mechanism for the regulation of tissue repair and regeneration."Biochem.J.. (In Press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木 宏治 (大内和雄 編集): "廣川タンパク質化学 第7巻 制御タンパク質-インヒビター"廣川書店 東京. 196 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木 宏治 (鈴木宏治, 一瀬白帝 編): "図説 分子病態学 3版"中外医学社 東京. 501 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishioka, j., et al.: "Protein C inhibitor potently inhibits activated hepatocyte growth factor activator : a possible mechanism for the regulation of tissue repair and regeneration"Biochem. j.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki, K., et al.: "Protective role of activated protein C in Lung and airway remodeling."Clit. Care Med.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi, T., et al.: "Characterization of a novel human protein C inhibitor gene transgenic mouse useful for studying the role of PCI in physiological and pathological condition."J. Thromb. Haemost.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] wakita, T., et al.: "Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma."Int. J. Cancer. 108. 516-523 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimoto, H., et al.: "Thrombin-activatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease."Am. J. Respir. Crit. Care Med.. 167. 1687-1694 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, S., et al.: "Activated protein C inhibits the expression of platelet-derived growth factor in the lung."Am. J. Respir. Crit. Care Med.. 167. 1416-1426 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gabazza, E.C., et al.: "Adenosine inhibits thrombin-induced expression of tissue factor on endothelial cells by a nitric oxide-mediated mechanism."Clin. Science. 102. 167-175 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui, H., et al.: "Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse."Am. J. Respir. Crit. Care Med.. 163. 1660-1668 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuneyoshi, N., et al.: "Expression and anticoagulant function of the endothelial cell protein C receptor (EPCR) in cancer cell lines."Thromb. Haemost.. 85. 356-361 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki, K.: "Protein C inhibitor (PAI-3) : structure and multi-function."Fibrinol.Proteol.. 14. 133-145 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, R., et al.: "Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable state."Am. J. Hematol.. 65. 35-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki, K., Hayashi, T: "Cis-elements required for expression of human protein C inhibitor (PCI) gene in HepG2 cells and its androgen-dependent expression in rat reproductive organs."Sem. Thromb. Hemost.. 26. 75-84 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuasa, H., et al.: "Bovine protein C inhibitor has a unique reactive site and can transiently inhibit plasmin."Thromb. Haemost.. 83. 262-267 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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