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Investigation of the regulatory mechanism of gene expression of human ecogenin/CTGF, a chondrocyte-derived growth factor.

Research Project

Project/Area Number 11671841
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionOkayama University

Principal Investigator

OHYAMA Kazumi (2001)  Okayama University, Dental School, Research Technician, 歯学部, 教務員 (00253021)

服部 高子 (1999-2000)  岡山大学, 歯学部, 助手 (00228488)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Tohru  Okayama University, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (30243463)
TAKIGAWA Masaharu  Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (20112063)
KUBOTA Satoshi  Okayama University, Graduate School of Medicine and Dentistry, Instructor, 大学院・医歯学総合研究科, 助手 (90221936)
大山 和美  岡山大学, 歯学部, 教務員 (00253021)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsCTGF / chondrocyte / gene expression / untranslated region / cis-element
Research Abstract

1) Research on transcriptional control of ecogenin/CTGF gene expression : We constructed a series of chimeric reporter gene constructs, in which the human CTGF promoter and its deletion mutants were linked upstream of firefly luciferase genes. Using these constructs, we comparatively analyzed their promoter activities via transient expression assay in chondrocytic HCS-2/8 cells. Then, we found a 110-bp DNA segment located at 88 bp-upstream of the transcription initiation site as a critical determinant of the enhanced CTGF gene expression in HCS-2/8 cells. Moreover, we found two enhancer elements that were active in HCS-2/8 cells. One of them was a known TGF-β response element, whereas the other was a novel one discovered in this study. Mutation of either element resulted in drastic decrease of the promoter activity in HCS-2/8 cells. It is especially interesting that binding counterpart(s) of the latter latter element was found to be present specifically in HCS-2/8 cells.
2) Research on … More post-transcriptional control of ecogenin/CTGF gene expression : We uncovered the strong repressive effect of the 1 kb-long 3'-untranslated region (UTR) of the ecogenin/CTGF gene on gene expression by comparatively evaluating the luciferase gene expression with or without the cis-linked 3'-UTR. Furthermore, we could identify an 84 base repressive cis-element by deletion analysis based on computer-associated structural prediction. Since this RNA element formed a stable secondary structure in solution, and the repressive function was highly dependent on the secondary structure forming potential, we entitled this element "cis-acting element of structure-anchored repression (CAESAR). Also recently, multiple stem-loop structure has been observed to be the structural determinant of CAESAR function. CAESAR did not display any effect outside of the transcribed region, and it did not affect the intracellular distribution of mRNA linked in cis. Therefore, CAESAR is thought to act at a step of mRNA translation without affecting the nuclear export of mRNA. Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Satoshi Kubota et al.: "Involvement of cis-acting repressive element(s) in the 3'-untranslated region of human connective tissue growth factor gene"FEBS Letters. 450. 84-88 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoshi Kubota et al.: "Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene : Similarities to retroviral RNA-protein interactions"Oncogene. 19. 4773-4786 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Seiji Kondo et al.: "Characterization of a mouse ctgf3'-UTR segment that mediates repressive regulation of gene expression"Biochemical and Biophysical Research Coommunucations. 278. 119-124 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoshi Kubota et al.: "Novel intracellular effects of human connective tissue growth factor expressed in Cos-7 cells"FEBS Letters. 474. 58-62 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takanori Eguchi et al.: "Regulatory mechanism of human connective tissue growth factor (CTGF/Hcs24) gene expression in a human chondrocytic cell line, HCS-2/8"Journal of Biochemistry. 130. 79-87 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoshi Kubota et al.: "Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells"Bone. 29. 155-161 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuyoshi Shimo et al.: "Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line"Cancer Letters. 174. 57-64 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Seiji Kondo et al.: "Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases"Carcinogenesis. (印刷中). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takashi Nishida et al.: "CTGF/Hcs24,a hypertrophic chondrocyte-specific gene product, stimulates the proliferation and differentiation but not hypertrophy of cultured articular cartilage cells"Journal of Cellular Physiology. (印刷中). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota, S., et al.: "Involvement of cis-acting repressive element(s) in the 3'-untranslated region of human connective tissue growth factor gene."FEES Letters. 450. 84-88 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota, S., et al.: "Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene : Similarities to retroviral RNA protein interactions."Oncogene. 19. 4773-4786 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kondo, S., et al.: "Characterization of a mouse ctgf 3'-UTR segment that mediates repressive regulation of gene expression."Biochem. Biophys. Res. Commun.. 278. 119-124 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota, S., et al.: "Novel intracellular effects of human connective tissue growth factor expressed in Cos-7 cells."FEBS Letters. 474. 58-62 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Eguchi, T., et al.: "Regulatory mechanism of human connective tissue growth factor (CTGF/Hcs24) gene expression in a human chondrocytic cell line, HCS-2/8."J. Biochem.. 130. 79-87 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kubota, S., et al.: "Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells."Bone. 29. 155-161 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimo, T., et al.: "Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line."Cancer Lett.. 174. 57-64 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kondo, S., et al.: "Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases."Carcinogenesis. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishida, et al.: "CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, stimulates the proliferation and differentiation but not hypertrophy of cultured articular cartilage cells."J. Cell. Physiol.. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takanori Eguchi et al.: "Regulatory mechanism of human connective tissue growth factor (CTGF/Hcs24) gene expression in a human chondrocytic cell line, HCS-2/8"Journal of Biochemistry. 130. 79-87 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Satoshi Kubota et al.: "Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells"Bone. 29. 155-161 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuyoshi Shimo et al.: "Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line"Cancer Letters. 174. 57-64 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Seiji Kondo et al.: "Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases"Carcinogeneses. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Satoshi Kubota et al.: "Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (dgf/hcs24) gene : Similarities to retroviral RNA-protein interactions."Oncogene. 19. 4773-4786 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seiji Kondo et al.,: "Characterization of a mouse ctgf 3'-UTR segment that mediates repressive regulation of gene expression."Biochemical and Biophysical Research Coommunucations. 278. 119-124 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Satoshi Kubota et al.: "Novel intracellular effects of human connective tissue growth factor expressed in Cos-7 cells."FEBS Letters. 474. 58-62 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Satoshi Kubota et al.: "Involvement of cis-acting repressive element(s) in the 3'-untranslated region of human connective tissue growth factor gene"FEBS Letters. 450. 84-88 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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