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REGULATORY MECHANISMS OF PLATELET-DERIVED GROWTH FACTOR BETARECEPTOR GENE EXPRESSION VIA CCAAT-BINDING PROTEINS.

Research Project

Project/Area Number 09670723
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionEHIME UNIVERSITY

Principal Investigator

KITAMI Yutaka  EHIME UNIVERSITY,EHIME UNIVERSITY HOSPITAL,ASSISTANT PROFESSOR, 医学部附属病院, 助手 (10234270)

Co-Investigator(Kenkyū-buntansha) OKURA Takafumi  EHIME UNIVERSITY,EHIME UNIVERSITY HOSPITAL,ASSISTANT PROFESSOR, 医学部附属病院, 助手 (40260385)
TAKATA Yasunori  EHIME UNIVERSITY,GRADUATE COURSE
NAKAMURA Michitsugu  EHIME UNIVERSITY,GRADUATE COURSE
FKUOKA Tomikazu  EHIME UNIVERSITY,GRADUATE COURSE
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsPDGF receptor / vascular smooth muscle cell / promoter activity / gene transcription / CCAAT-binding protein / NF-Y family / C / EBP family / gene therapy / 血小板由来成長因子β-受容体 / 5'-上流域 / 細胞増殖 / 5^1-上流域 / NF-Y
Research Abstract

Platelet-derived growth factor (PDGF) is one of major growth factors on cellular development or hypertrophy in vascular smooth muscle cells (VSMC). PDGF is known to become physiologically active when it binds to its specific receptor, alpha or beta. -Main purpose of this study is to elucidate regulatory mechanisms of PDGF n-receptor (PDGFRB) gene expression in VSMC.Functional analyses of PDGFRB gene promoter revealed that PDGFRB gene transcription is mainly regulated by two important cis-elements located at -150 through -121 (designated R30) and at -67 through -61 (CCAAT box, designated C67). DNA-binding studies indicated that NF-Y family (especially NF-YC), which belongs to one of CCAAT-binding protein families, is specifically interacted with the C67 sequence and positively regulates the transcriptional activity of the PDGFRB gene. On the other hand, R30, which contains a negative regulatory element (NRE), negatively control the gene expression under a tissue-specific manner. Further … More more, to gain a direct evidence that these cis-elements are functional active in VSMC, effects of sequence-specific "decoy" oligodeoxynucleotide (OUN) for these two sequences on intrinsic PDGFPB mRNA expression were also investigated. Either 'decoy' ODN for R30 or C67 significantly suppressed intrinsic PDGFRB mRNA expression in VSMC indicating that these two elements can act as a functional promoter and/or an upstream control element of PDGFRB gene transcription. Previously, we have also determined the importance of another CCAAT-binding family, CCAAT/enhancer-binding proteins (C/FBP) family, on the transcriptional activity of the PDGF alpha-receptor (PDGFRA) gene in VSMC.From these two studies, we strongly postulate the hypothesis that CCAAT-binding proteins including NF-Y and C/EBP play a pivotal role in the transcriptional regulation of the genes related to the vascular development or remodeling in vivo. Furthermore, CCAAT boxs and their binding factor families may become useful candidates for the gene therapy of atherosclerotic and restenotic lesions in the vessel wall. Less

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kitami Y,Fukuoka T,Hiwada K,Inagami T: "A high level of CCAAT-enhancer binding protein-δ expression is a major determinant for markedly elevated differential gene expression of the platelet-derived growth factor -α receptor in vascular smooth muscle cells of genetically hypertensive rats." Circulation Research. 84・1. 64-73 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takata Y,Kitaml Y,Fukuoka T,Okura T,Hiwada K: "A novel cis-element for tissue-specific transcription of rat platelet-derived growth factor β-receptor gene." Hypertension. 33・1. 298-302 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitami Y,Fukuoka T,Okura T,Takata Y,Maguchi M,Igase M,Kohara K,Hiwada K: "Molecular structure and function of rat platelet-derived growth factor β-receptor gene promoter." Journal of Hypertension. 16・4. 437-445 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuoka T,Kitami Y,Kohara K,Hiwada K: "Molecular structure and function of rat CCAAT-enhancer binding protein-delta gene promoter." Biochemical Biophysical Research Communications. 231・1. 30-36 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高田康徳,北見 裕,福岡富和,大蔵隆文,間口元文,伊賀瀬道也,姜 一農,小原克彦,日和田邦男: "血管平滑筋細胞における血小板成長因子β-受容体遺伝子の発現調節." 血圧. 5.3. 288-296 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 福岡富和,北見 裕,大蔵隆文,間口元文,伊賀瀬道也,小原克彦,日和田邦男: "血管平滑筋細胞における核内転写制御因子C/EBPδ遺伝子の発現調節." 血圧. 4・3. 265-271 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitami Y, Fukuoka T, Hiwada K, Inagami T.: "A high level of CCAAT-enhancer binding protein-delta is a major determinant for markedly elevated differential gene expression of the platelet-derived growth factor alpha-receptor in vascular smooth muscle cells of genetically hypertensive rats." Circulation Research. 84 (1). 64-73 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takata Y, Kitami Y, Fukuoka T, Okura T, Hiwada K.: "A novel cis element for tissue specific transcription of rat platelet-derived growth factor beta-receptor gene." Hypertension. 33 (1). 298-302 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitami Y, Fukuoka T, Okura T, Takata Y, Maguchi M, Igase M, Kohara K, Hiwada K.: "Molecular structure and function of rat platelet-derived growth factor beta-receptor gene promoter." Journal of Hypertension. 16 (4). 437-445 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuoka T, Kitami Y, Kohara K, Hiwada K.: "Molecular structure and function of rat CCAAT-enhancer binding protein-delta gene promoter." Biochem Biophys Res Commun. 231 (1). 30-36 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takata Y, Kitami Y, Fukuoka T, Okura T, Maguchi M, Igase M, Jiang Y, Kohara K, Hiwada K.: "Regulatory mechanisms of platelet-derived growth factor beta-receptor gene expression in vascular smooth muscle cells." Blood Pressure (in Japanese). 5 (3). 288-296 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuoka T, Kitami Y, Okura T , Maguchi M, Igase M, Kohara K, Hiwada K.: "Regulatory mechanisms of a nuclear transcriptional factor, C-EBPdelta, gene expression in vascular smooth muscle cells." Blood Pressure (in Japanese). 4 (3). 265-271 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitami Y,Fukuoka T,Okura T,Takata Y,Maguchi M,Igase M,Kohara K,Hiwada K: "Molecular structure and function of rat platelet-derived growth factor β-receptor gene promoter." Journal of Hypertension. 16・4. 437-445 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukuoka T,Kitami Y,Kohara K,Hiwada K: "Molecular structure and function of rat CCAAT-enhancer binding protein-delta gene promoter." Biochemical Biophysical Research Communications. 231・1. 30-36 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高田康徳、北見 裕、福岡富和、大蔵隆文、間口元文、伊賀瀬道也、姜 一農、小原克彦、日和田邦男: "血管平滑筋細胞における血小板成長因子β-受容体遺伝子の発現調節." 血圧. 5・3. 288-296 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 福岡富和、北見 裕、大蔵隆文、間口元文、伊賀瀬道也、小原克彦、日和田邦男: "血管平滑筋細胞における核内転写制御因子C/EBPδ遺伝子の発現調節." 血圧. 4・3. 265-271 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 福岡富和, 北見裕, 大蔵隆文, 間口元文, 伊賀瀬道也, 小原克彦, 日和田邦男: "血管平滑筋細胞における核内転写制御因子C/EBPδ遺伝子の発現調節" 血圧. 4・3. 265-271 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukuoka T, Kitami Y, Kohara K, Hiwada K: "Molecular structure and function of rat CCAAT-enhancer binding protein-delta gene promoter." Biochem Biophys Res Commun. 231/1. 30-36 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kitami Y, Fukuoka T, Okura T, Takata Y, Maguchi M, Igase M, Kohara K, Hiwada K: "Molecular structure and function of rat platelet-derived growth factor β-receptor gene promoter." J Hypertens. 16(in press). (1998)

    • Related Report
      1997 Annual Research Report

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

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