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1995 Fiscal Year Final Research Report Summary

Transcriptional Regulation of Thrombomodulin by Interactions of the Gene Sequences with Nuclear Proteins

Research Project

Project/Area Number 06672202
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionFaculty of Pharmaceutical Sciences, Teikyo University

Principal Investigator

HORIE Shuichi  Teikyo University, Faculty of Pharmaceutical Sciences, Department of Clinical Biochemistry, Lecturer, 薬学部, 講師 (60157063)

Project Period (FY) 1994 – 1995
KeywordsThrombomodulin / Retinoic Acid / Transcription / Nuclear Receptor / RARE / Spl / CAT Assay / BxPC-3 Cell
Research Abstract

We reported that thrombomodulin (TM) , the anticoagulant cofactor for activation of protein C,was up-regulated by treatment of endothelial cells with all-trans retinoic acid (RA) throgh the transcriptional acceleration. In the present investigation, the transcriptional regulatory sequence of the 5'-untranslated region of TM gene studied by transient expression assay in human pancreas BxPC-3 cells. Deletion mutants of plasmid constructs containing the TM promoter and chloramphenicol acetyltransferase (CAT) reporter gene exhibited that presence of proximal (-202 to 207) and distal (-1515 to -1531) RA-responsive regions. The distal one contains RA response element and the proximal one contains Spl site in the DNA sequence. The both sequences were additive in the increase in promoter activity by RA and mutations introduced into each sequence confirmed the functional response with RA-treatment. Transactivation study showed that cotransfection of the plasmid containing both the sequences with expression plasmid for RA receptor, such as RAR-alpha, -beta, -gamma and RXR-alpha, did not enhance RA-dependent promoter activity, though RAR-beta mRNA increased in BxPC cells treated with RA.Gel retardation experiment indicated the Spl protein not AP2 protein interacted with the Spl sequence where not with the Spl-deleted sequence. By treatment of the cells with RA time-dependent increases in mRNA levels of Spl, SPR-l and SPR-2 were observed. We concluded that two sites of genomic DNA regions particpated in the RA-dependent augmentation of TM gene expression.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Shuichi Horie: "Enhancement of thrombin-thrombomodulin-catalyzed protein Cactivation by phosphatidylethanolamine containing unsaturated fatty acids : Possible physiological significance of phosphatidylethanolamine in anti-coagulant activity of thrombomodulin" Biochem.J.301. 683-691 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Keiichiro Kizaki: "Thrombomodulin induction by all-trans retinoic acid is independent of HL-60 differentiation to neutrophilic cells" Thromb.Haemost.72. 573-577 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堀江修一: "血管壁からみた血栓準備状態(An Aspect of Pre-thrombotic State on Vascular Endothelium)" 脈管学. 34. 353-359 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Hamada: "The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells" Blood. 86. 225-233 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hidemi Ishii: "Oxidized low density lipoprotein reduces thrombomodulin transcription in cultured human endothalial cells through degradation of the lipoprotein in lysosomes" J.Biol.Chem.(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堀江修一 著, 須賀哲弥 編: "病態生理化学(先天性代謝異常症)" 朝倉書店, 24 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shuichi HORIE,Hidemi ISHI,Hideyuki HARA & Mutsuyoshi KAZAMA: "Enhancment of thrombin-thrombomodulin-catalyzed protein C activation by phosphatidylethanolamine containing unsaturated fatty acids : Possible physiological significance of phosphatidyl-ethanolamine in anti-coagulant activity of thrombomodulin." Biochem.J.301. 683-691 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Keiichiro KIZAKI,Hidemi ISHII,Shuichi HORIE & Mutsuyoshi KAZAMA: "Retinoic acid stimulates expression of thrombomodulin, a cell surface anticoagulant glycoprotein, on human endothelial cells : Difference between up-regulation of thrombomudulin by retinoic acid and cyclic AMP." Thromb.Haemost.72. 573-577 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] ShuichiHORIE,Keiichiro KIZAKI,Hidemi ISHII & Mutsuyoshi KAZAMA: "An aspect of pre-thrombotic state on vascular endothelium." Myakukangaku. 34. 353-359 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroyuki HAMADA,Hidemi ISHII,Katsufumi SAKYO,Shuichi HORIE,Katsuyuki NISHIKI & Mutsuyoshi KAZAMA: "The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells." Blood. 86. 225-233 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hidemi ISHII,Keiichiro KIZAKI,Shuichi HOIE & Mutsuyoshi KAZAMA: "Oxidized low density lipoprotein reduces thrombomodulin transcription in cultured human endothelial cells throgh degradation of the lipoprotein lysosomes." J.Biol.Chem. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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