| Project/Area Number |
03671064
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
HORIE Shuichi Faculty of Pharmaceutical Sciences, Department of Clinical Biochemistry, Lecturere, 薬学部, 講師 (60157063)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Hidemi Faculty of Pharmaceutical Sciences, Department of Clinical Biochemistry, Assista, 薬学部, 助教授 (50102710)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Thrombomodulin / Retinoic Acid / Regulation of Expression / HL-60 / Cell Differentiation / Endothelial Cell / CAT Assay / Nuclear Receptor / ビタミンA酸 / 凝固調節 / 甲状腺ホルモン / レセプター / レセプタ- |
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| Research Abstract |
Thrombomodulin(TM) is a surface glycoprotein on endothelial cells, and represents one of the most valuable regulatory factors in the anticoagulant system. The present study was investigated the effect of retinoic acid (RA) on the expression of TM and its regulatory mechanism in endothelial cells and in HL-60 cells during its differentiation. Results indicated that RA caused to the increase in TM mRNA level to up-regulate TM expression, and suggested that RA-induced up-regulation of TM on endothelial cells was independent of cyclic AMP level. We found that RA effectively counteracts the inflammatory cytokines-induced prothrombotic properties of endothelial cells, caused by downregulating TM and inducing tissue factor expression. Thus, RA may be considered for evaluation not only as an antileukemic, but also as an antithrombotic drug. On the other hand, trace amounts of TM antigen were induced in neutrophilic cells differentiated from HL-60 by treatment with RA and found that different levels of TM were induced in monocytic, macrophagic and neutrophilic cells differentiated from HL-60 cells. From the study of the promoter activity of TM it was suggested that RA-dependent increase in TM transcription in cells was associated with the nucleotide sequence located in the 5'-flanking region of the TM gene. Alternatively, it is considered that the regulatory mechanism of TM expression in cells treated with RA is dependent on the amount of functional RA receptor protein in each cell.
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