| Project/Area Number |
11470209
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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 | Nagoya University |
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Principal Investigator |
SAITO Hidehiko School of Medicine, Nagoya University, Professor, 医学部, 教授 (20153819)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Koji School of Medicine, Nagoya University, Medical Staff, 医学部, 医員
KOJIMA Tetsuhito School of Medicine, Nagoya University, Professor, 医学部, 教授 (40161913)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2000: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1999: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | Thrombosis / Sepsis / TFPI / TNF-alpha / IL-1 / Gene Expression / Fibrin deposition / 老化 / 遺伝子発現 / 血液凝固 / 線溶能 |
|---|
| Research Abstract |
Tissue factor pathway inhibitor (TFPI) is the protease inhibitor that regulates the extrinsic coagulation pathway initiated by the factor VIIa/TF complex. In this study, we first investigated tissue distribution of TFPI mRNA in the mouse and found that TFPI mRNA expression level was by far the highest in the lung, followed by the heart, adrenal, and adipose tissue. Since little has been known concerning the regulation of TFPI gene expression in vivo, we further analyzed the changes in the TFPI mRNA level in murine tissues after intraperitoneal injection of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1). LPS and TNF-alpha dramatically decreased TFPI mRNA expression in four tissues examined (e.g., lung, heart, kidney, and adipose tissue, in which fibrin deposition were observed), whereas the suppressive effect of IL-1 on TFPI mRNA was limited. The down-regulation of TFPI mRNA expression by LPS and TNF-alpha was also observed in cultured mouse endothelial cells and in cardiomyocyte cell lines. The decreased TFPI gene expression by LPS and TNF-alpha in tissues and in the specific cell types may contribute to an increase in the local procoagulant potential, resulting in the thrombotic tendency under septic and/or inflammatory conditions.
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