2006 Fiscal Year Final Research Report Summary
Molecular pathobiological studies on anti-coagulant protein C pathway which is essential for the vital functions
| Project/Area Number |
17390276
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Mie University |
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Principal Investigator |
SUZUKI Koji Mie University, Graduate School of Medicine, Department of Molecular pathobiology, Professor, 大学院医学系研究科, 教授 (70077808)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Tatsuya Mie University, Graduate School of Medicine, Department of Molecular pathobiology, Associate Professor, 大学院医学系研究科, 助教授 (00242959)
OKAMOTO Takayuki Mie University, Graduate School of Medicine, Department of Molecular pathobiology, Assistant Professor, 大学院医学系研究科, 助手 (30378286)
GABAZZA Esteban Mie University, Graduate School of Medicine, Department of Molecular pathobiology, Professor, 大学院医学系研究科, 教授 (00293770)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Anticoagulant protein C pathway / Activated protein C / Protein S / Protein C inhibitor / Thromb omodulin / Inflammation / Tissue remodeling / Fertilization |
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| Research Abstract |
In this research project, we performed molecular pathobiological studies on the factors involved in the anti-coagulant protein C pathway which is essential for the vital functions. We obtained several new findings, described as follows:
First we found that there are different metabolic correlations of thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) in non-obese type 2 diabetic patients. Secondly we demonstrated that lipopolysaccharide-induced decreased protein S expression in liver cells is mediated by MEK/ERK signaling and NFkappaB activation: This phenomenon is involvement of membrane-bound CD14 and toll-like receptor-4. Then, we showed that protein C inhibitor (PCI) plays a protective role in monocrotaline-induced pulmonary hypertension. Further, we demonstrated that deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse by using tenascin C deficient mice. Successively we demonstrated that intratracheal gene transfer of tissue factor pathway inhibitor (TFPI) attenuates pulmonary fibrosis by in vitro and in vivo studies. Further, we showed that TAFI deficiency attenuates bleomycin-induced lung fibrosis by using TAFI knockout mice. Furthermore, we demonstrated that there is a differential regulation of protein S expression in hepatocytes and sinusoidal endothelial cells in rats with cirrhosis. Moreover, we described a review in a series of reviews on seminal plasma clotting system that the interaction among PCI, prostate-specific antigen (PSA), and the semenogelin system. Successively, we found that human PCI inhibits breast cancer cell growth, metastasis and angiogenesis independently of its protease inhibitory activity. Lastly, we demonstrated that human PCI also plays a role as an inhibitor of activated hepatocyte growth factor activator in the liver regeneration.
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Research Products
(11 results)
