| Project/Area Number |
12357017
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory medicine
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| Research Institution | Mie University |
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Principal Investigator |
SUZUKI Koji Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70077808)
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| 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
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| Project Period (FY) |
2000 – 2002
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| Keywords | liver regeneration / protein C inhibitor / Hepatocyte growth factor activator / hepatocyte growth factor / activated protein C / inflammation / protein chip-ELISA / molecular markers for tissue regeneration |
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| 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.
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