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Regulatory mechanism to tissue factor gene expression by its methylation/demethylation

Research Project

Project/Area Number 09671108
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NAKAMURA Shin  Primate Research Institute, KYOTO UNIVERSITY,Instructor, 霊長類研究所, 助手 (10101255)

Co-Investigator(Kenkyū-buntansha) WADA Hideo  Mie University, School of Medicine, Instructor, 医学部, 助手 (40158704)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsTissue Factor / Methylation / Demethylation / Gene expression / Regulatory mechanism / Seminal vesicle / Testosterone / TF-mRNA / 精嚢 / mRNA発現 / 遺伝子発現制御 / CpG島 / 脱分化
Research Abstract

Tissue Factor (TF) is a factor VII/VIIa receptor that initiates blood coagulation. TF is suggested to have other functions such as involvement in embryogenesis, angiogenesis, tumor metastasis, and/or signal transdution. TF gene expression is regulated by several is-elements of AP-1, kappaB, SP-1 and Erg-1 and transcriptional factors to bind these cis-elements. Another regulatory machinery to TF gene expression is expected because there are a lot of CG island specific site for methylation at cytosine residues.
In this studies we examined a possible regulation mechanism of TF gene expression through methylation and/or demethylation of its promoter region. We also investigated a relationship between differentiation and de-differentiation/transformation of several cells and methylation/ demethylation of TF gene.
We established a competitive RT-PCR which is enable to quantitative measurement of TF m-RNA expressed in several normal or transformed cells using specific primer sets. We also established sensitive sandwich enzyme-linked immuno-sorbent assay to measure TF antigen produced in these cells.
In normal blood cells monocytes and granulocytes expressed TF but lymphocytes did not. Marked different expression of TF gene in monkey male reproductive tissues. Seminal vesicle specifically expressed very high level of TF-mRNA.These suggest TF gene expression should regulated by methylation/demethylation during differentiation of leukocytes from common precursor and tissue speculation.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] R.Watanabe, et al (including S.Nakamura): "Long-Term Follow-up of Hemostatic Molecular Markers during Remission Induction Thetapy with All-trans Retinoic Acid for Acute Promyelocytic Leukemia" Thromb. Haemost.77. 641-645 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Kaikita, et al (including S.Nakamura): "Tissue Factor Expression on Macrophages in Coronary Plaques in Patients with Unstable Angina." Arterioscler. Thromb. Vasc. Biol.17. 2232-2237 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hirashima S. Nakamura: "Cerebrospinal Fluid Tissue Factor and Thrombin-Antithrombin III Complex as Indicators of Tissue Injury after Subarachnoid Hemorrhage," Stroke.28. 1666-1670 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H. Suefuji, et al (including S.Nakamura): "Increased Plasma Tissue Factor Levels in Acute Myocardial Infarction," Am. Heart j.134. 253-259 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J. M. Morrissey, et al (including S. Nakamura): "CD142 (tissue factor) Workshop panel report" Leukocyte Typing IV, White Cell Differentiation Antigens. 742-746 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Matsumoto, et al (including S.Nakamura): "Fluid Shear Stress Attenuates Tumor Necrosis Factor-Induced Tissue Factor Expression in Cultured Human Endothelial Cells," Blood. 91. 4164-4172 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] R.Watanabe, M.Murata, N.Takayama, M.Tokuhira, M.Kizaki, S.Okamoto, Y.Kawai, K.Watanabe, H.Murakami, M.Kikuchi, S.Nakamura, Y.Ikeda: "Long-Term Follow-up of Hemostatic Molecular Markers during Remission Induction Thetapy with All-trans Retinoic Acid for Acute Promyelocytic Leukemia." Thromb.Haemost.77. 641-645 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hirashima, S.Nakamura, M.Suzuki, M.Kurimoto, S.Endo, A.Ogawa, A.Takaku: "Cerebrospinal Fluid Tissue Factor and Thrombin-Antithrombin III Complex as Indicators of Tissue Injury after Subarachnoid Hemorrhage." Stroke. 28. 1666-1670 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Kaikita, H.Ogawa, H.Yasue, M.Takeya, K.Takahashi, T.Saito, K.Hayasaka, K.Horiuchi, A.Takizawa, Y.Kamikubo, S.Nakmamura: "Tissue Factor Expression on Macrophages in Coronary Plaques in Patients with Unstable Angina" Arterioscler.Thromb.Vasc.Biol.17. 2232-2237 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hirashima, S.Nakamura, S.Endo, N.Kuwayama, Y.Naruse, A.Takaku: "Evaluation of Platelet Activating Factor, Inflammatory Cytokines, and Coagulation Factors in the Internal Jugular Vein of Patients with Subarachniod Hemorrhage." Neurochemical Res.22. 1249-1255 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Suefuji, H.Ogawa, H.Yasue, K.Kaikita, H.Soejima, T.Motoyama, Y.Mizuno, S.Oshima, T.Saito, I.Tsuji, K.Kumeda, Y.Kamikubo, S.Nakamura.: "Increased Plasma Tissue Factor Levels in Acute Myocardial Infarction." Am.Heart J.134. 253-259 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.M.Morrissey, H.Agis, S.Albrecht, F.Dignat-George, T.S.Edgington, T.Luther, M.Muller, M.Mutin, S.Nakamura, P.Valent, G.M.Vercellotti: "CD142 (tissue factor)" Workshop panel report, Leukocyte Typing IV,White Cell Differentiation Antigens. eds., T.Kishimoto, et al.742-746 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Misumi, H.Ogawa, H.Yasue, H.Soejima, H.Suefuji, K.Nishiyama, K.Takagoe, K.Kugiyama, I.Tsuji, K.Kumeda, S.Nakamura: "Comparison of Plasma Tissue Factor Levels in Unstable and Stable Angina Pectoris" Am.J.Cardiol.81. 22-26 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Matsumoto, Y.kawai, I-60. K.Watanabe, K.Sakai, M.Murata, M.Handa, S.Nakamura, Y.Ikeda: "Fluid Shear Stress Attenuates Tumor Necrosis Factor-Induced Tissue Factor Expression in Cultured Human Endothelial Cells" Blood. 91. 4164-4172 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Wada, Y.Mori, M.Shimura, k.Hiyoyama, M.Loka, T.Nakasaki, M.Nishikawa, M.Nakano, K.Kumeda, T.Kaneko, S.Nakamura, H.Shiku.: "Poor Outcome in Disseminated Intravascular Coagulation or Thrombotic Thrombocytopenic Purpura Patients with Sever Vascular Ebdothelial Cell Injuries." Amer.J.Hematol.58. 189-194 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.kagawa, Y.komiyama, S.Nakamura, T.Miyake, Y.Miyazaki, K.Hamamoto, M.Masuda, H.Takahashi, S.Nomura, S.Fukuhara: "Expression of Functional Tissue Factor on Small Vesiclee of Lipopolysaccharide-stimulated Human Vascular Endothelial Cells" Thromb.Res.91. 297-304 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] C.Shgemori, H.Wada, K.Matsumoto, H.Shiku.S.Nakamura, H.Suzuki: "Tissue Factor Expression and Metastic Potentail of Colorectal Cancer" Thromb.Haemost.80. 894-898 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] R.Watanabe,et al.: "Long-Term Follow-up of Hemostatic Molecular Markers during Remission Induction Therapy with All-trans Retinoic Acid for Acute Promyelocytic Leukemia" Thromb.Haemost.77. 641-645 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Kaikita,et al.: "Tissue Factor Expression on Macrophages in Coronary Plaques in Patients with Unstable Angina." Arterioscler.Thromb.Vasc.Biol.17. 2232-2237 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Hirashima,S.Nakamura: "Cerebrospinal Fluid Tissue Factor and Thrombin-Antithrombin III Complex as Indicators of Tissue Injury after Subarachnoid Hemorrhage" Stroke. 28. 1666-1670 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Suefuji,et al.: "Increased Plasma Tissue Factor Levels in Acute Myocardial Infarction" Am.Heart J.134. 253-259 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.M.Morrissev.et al.: "CD142(tissue factor)Workshop panel report" Leukocyte Typing IV,White Cell Differentiation Antigens. 742-746 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Matsumoto,et al.: "Fluid Shear Stress Attenuates Tumor Necrosis Factor-Induced Tissue Factor Expression in Cultured Human Endothelial Cells" Blood. 91. 4164-4172 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe,R, et al: "Long term Follow-up of Hemostatic Molecular Maphers oluring Remission Induction Thetcgy with ATRA for Acute Leukenlia" Thromb,Halmost. 77. 641-645 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kim,H-S., et al: "Nucleaticle Sequence of cDNA and Gene Expresion of Testis-Specific Protein Y in the Japanese Monkey" Zocl.Sci.14. 609-614 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirashima,Y., et al: "Cerebrospinal Fliud Tissue Factor and Thrombin-Antithrombin IV Conplix." Stroke. 28. 1666-1670 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kaikita,K., et al.: "Tissue Factor Expression on Macrophages in Cownary Plaque in patients with Uastable Angrh" Arter.Thromb.Vasc.Biol.17. 2232-2237 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirashima,Y., et al: "Elevation f Platetet Activating Factor,Inflammatory Cytakiney,and Coagulrtion Factas in the Internal Jugeclor." Neurochem.Res.22. 1249-1255 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morrissey,JM, et al: "CD142(Tissue factor)Workshop Panel report" Leucocyte Typing VI. 742-746 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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