A novel function of thrombin activatable fibrinolysis inhibitor during rat liver regeneration and in growth-promoted hepatocytes in primary culture
| Project/Area Number |
17580084
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | Nihon University |
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Principal Investigator |
SEKT Taiichiro Nihon University, College of Bioresource Sciences, Associate Professor (20187834)
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| Co-Investigator(Kenkyū-buntansha) |
ARIGA Toyohiko Nihon University, College of Bioresource Sciences, Professor (50096757)
OGIHARA Jun Nihon University, College of Bioresource Sciences, Assistant Professor (50256830)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | hepatocyte / liver / TAFI / fibrinolvsis / plasminogen / siRNA / TAF1 / regeneration |
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| Research Abstract |
Thrombin-activatable fibrinolysis inhibitor (TAFI) exhibits anti-fibrinolytic activity by removing C-terminal lysine residues from fibrin or plasminogen receptor proteins on the cellular surface, and plays an important role in the regulation of fibrinolysis. In this study, we examined the regulation of TAFI in hepatocytes during liver regeneration, and revealed its pivotal role in hepatocyte proliferation. In rat models, partial hepatectomy or CC1_4-induced acute liver injury suppressed the levels of plasma TAFI activity and hepatic TAFI mRNA, whereas this operation markedly increased both the hepatic plasmin activity and the level of proliferating cell nuclear antigen (PCNA). In primary cultures of rat hepatocytes, the TAFI mRNA level was decreased under growth-promoting culture conditions. Treatment of the hepatocytes with TAFI siRNA increased the amount of plasmin on the hepatocytes and promoted hepatocyte proliferation. We concluded that TAFI regulates plasmin activity through its enzymatic activity whereby it reduces the plasminogen-binding capacity of the hepatocytes. The TAFI gene expression is down-regulated for hepatocyte proliferation to occur by producing a fibrinolytic microenvironment suitable for cell growth. This is the first report on the role of TAFI in the pericellular fibrinolysis necessary for cellular proliferation.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Annexin A3 expression increases in hepatocytes and is regulated by hepatocyte growth factor in rat liver regeneration2008
Author(s)
Harashima, M., Harada K., Ito Y., Hyuga, M., Seki, T., Ariga, T., Yamaguchi, T., Niimi, S
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Journal Title
J Biochem 143(4)
Pages: 537-545
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Annexin A3-expressing cellular phenotypes emerge from necrotic lesion in the pericentral area in 2-acetylaminofluoren/carbon tetrachloride-treated rat livers. Epub 2007 Dec 72007
Author(s)
Ito, Y., Watanabe, T., Nagatomo, S., Seki, T., Niimi, S., Ariga, T
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Journal Title
Biosci Biotechnol Biochem 71(12)
Pages: 3082-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Change in annexin A3 expression by regulatory factors of hepatocyte growth in primary cultured rat hepatocytes2006
Author(s)
Harashirna, M., Niimi, S., Koyanagi, H., Hyuga, M., Noma, S., Seki, T., Ariga, T., Kawanishi, T., Hayakawa, T
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Journal Title
Biol Pharm Bull 29(7)
Pages: 1339-43
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Formation of rat hepatocyte spheroids on agarose2005
Author(s)
Hasebe, Y., Okumura, N., Koh T., Kazama, H., Watanabe, G., Seki, T., Ariga, T
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Journal Title
Hepatol Res 32(2)
Pages: 89-95
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A role of surface-bound plasminogen in the liver regeneration in rat2007
Author(s)
N., Okumura, Y., Maeda, S., Shimonishi, T., Seki, T., Ariga
Organizer
The International Society on Thrombosis and Haemostasis XXth Congress (ISTH2007)
Place of Presentation
at Geneva PALEXPO, Switzerland
Year and Date
2007-07-11
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Regulation of thrombin-activatable fibrinolysis inhibitor(TAFI)gene expression in growth-promoted hepatocytes andregeneration2005
Author(s)
N. Okumura, T. Koh, Y. Hasebe, G.Watanabe, A. Yashiki, A. Seno, T.Suzuki, S. Niimi, T. Kawanishi, T.Hayakawa, T. Seki, T. Ariga:
Organizer
The International Society on Thrombosis and Haemostasis XXth Congress(ISTH2005)
Place of Presentation
Sydney Convention and Exhibition Centre,Australia
Year and Date
2005-08-09
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] Regulation of thrombin-activatable fibrinolysis inhibitor (TAFI) gene expression in growth-promoted hepatocytes and role of TAFI in liver regeneration2005
Author(s)
N., Okumura, T., Koh, Y., Hasebe, G., Watanabe, A., Yashiki, A., Seno, T., Suzuki, S., Niimi, T., Kawanishi, T., Hayakawa, T., Seki, T., Ariga
Organizer
The International Society on Thrombosis and Haemostasis XXth Congress (ISTH2005)
Place of Presentation
at the Sydney Convention and Exhibition Centre, Australia
Year and Date
2005-08-09
Description
「研究成果報告書概要(欧文)」より
Related Report
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