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Studies on Drug Permeation in Placental Barrier by RNA Interference

Research Project

Project/Area Number 17590136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionShowa Pharmaceutical University

Principal Investigator

WATANABE Yoshiteru  Showa Pharmaceutical University, Professor, 薬学部, 教授 (70175131)

Co-Investigator(Kenkyū-buntansha) KONDOH Masuo  Osaka University, Graduate School, Associate Professor, 大学院・薬学研究科, 准教授 (50309697)
FUJII Makiko  Showa Pharmaceutical University, Associate Professor, 薬学部, 准教授 (50199296)
KOIZUMI Naoya  Showa Pharmaceutical University, Research Associate, 薬学部, 助教 (80433845)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsplacental barrier / drug permeation / RNA interference / gene delivery system / transgene expression / trophoblast cell / pharmacology / 遺伝子 / 薬物透過機構
Research Abstract

To elucidate drug permeation mechanism by transporters in placental barrier, we positively studied the establishment of RNA interference (RNAi) technique using viral and nonviral vector systems. In a preliminary study, RNAi using fiber-modified Ad vectors, it was suggested that the combination of fiber-modified Ad vectors containing polylysine peptide and RNAi is an effective tool for study of biological and physiological mechanism such as adipogenesis in adipose. Ad vector-mediated RNAi for peroxisome proliferator-activated receptor (PPAR) γ should also be useful to clarify the biological role of the PPAR γ pathway in various tissues. This finding led us to investigate RNAi using Ad vectors in placental barrier functions. On the other hand, we studied transgene activity of Ad vector containing Arg-Gly-Asp (RGD) motif in the fiber protein (Ad-RGD vector) during differentiation of human cytotrophoblast BeWo cells into syncytiotrophoblast-like cells. Ad-RGD vector had no influence on dif … More ferentiation and had a 2.5 fold higher transduction activity than that of the conventional Ad vector. Thus, Ad-vRGD vector can be a powerful tool for gene transfer experiments in syncytiotrophoblast cells. Subsequently, we investigated characteristics of transcription-regulatory elements for gene expression from plasmid vectors in human trophoblast cell lines BeWo and JAR cells. It was found that insertion of intron elements enhanced transcriptional activities in the following order: intron A>hybrid β-globin-immunoglobin intron>no intron. We also found that gene expression level can be controlled by selecting the expression cassette. These results may be useful for further studies on construction of siRNA expression cassette by polymerase II promoter. For induction of transporters, we observed an induction of zinc transporters by forskolin in human trophoblast BeWo cells. A function of transporter in placenta during pregnancy, the mechanism of zinc release from the placenta into fetal circulation is not well understand. Treatment of BeWo cells with forskolin, a representative inducer of differentiation of BeWo cells cytotrophoblast into syncytiotrophoblast, resulted in morphological changes of BeWo cells and elevated Zn transporter 1, 2 and 4 mRNA levels. Several findings in this project should be useful for studies aimed at analysis of transporters in placenta using RNAi. We will continue further studies on RNAi of transporters by delivery of viral and nonviral vectors. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (11 results)

All 2006 2005

All Journal Article (11 results)

  • [Journal Article] Efficient Gene Transfer into Differentiated Human Trophoblast Cells With Adenovirus Vector Conthining RGD Motif in the Fiber Protein.2006

    • Author(s)
      Koizumi N, Mizuguchi H, Watanabe Y., et al.
    • Journal Title

      Biol. Pharm. Bull. 29

      Pages: 1297-1299

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characteristics of transcription-regulatory elements for gene expression from plasmid vectors in human trophoblast cell lines.2006

    • Author(s)
      Komiya E, Kondoh M, Watanabe Y., et al.
    • Journal Title

      Placenta 27

      Pages: 934-938

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of zinc transporters by forskolin in human trophoblast BeWo cells.2006

    • Author(s)
      Asano N, Kondoh M, Watanabe Y., et al.
    • Journal Title

      Reprod. Toxicol. 21

      Pages: 285-291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Efficient gene transfer into differentiated human trophoblast cells with adenovirus vector containing RGD motif in the fiber protein.2006

    • Author(s)
      Koizumi, N., Mizuguchi, H., Kondoh, M., Watanabe, Y, et al.
    • Journal Title

      Biol. Pharm. Bull. 29

      Pages: 1297-1299

    • NAID

      110005602289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characteristics of transcription-regulatory elements for gene expression from plasmid vectors in human trophoblast cell lines.2006

    • Author(s)
      Komiya, E., Kondoh, M., Mizuguchi, H., Watanabe, Y, et al.
    • Journal Title

      Placenta 27

      Pages: 934-938

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of zinc transporters by forskolin in human trophoblast BeWo cells.2006

    • Author(s)
      Asano, N., Kondoh, M., Utoguchi, N., Watanabe, Y, et al.
    • Journal Title

      Reprod. Toxicol. 21

      Pages: 285-291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Characteristics of transcription-regulatory elements for gene expression from plasmid vectors in human trophoblast cell lines.2006

    • Author(s)
      Komiya E, Watanabe T., et al.
    • Journal Title

      Placenta. 9-10

      Pages: 934-938

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Efficient Gene Transfer into Differentiated Human Trophoblast Cells with Adenovirus Vector Containing RGD motif in the Fiber Protein2006

    • Author(s)
      Koizumi N., Watanabe T., et al.
    • Journal Title

      Bio.Pharm.Bull. 29(In press)

    • NAID

      110005602289

    • Related Report
      2005 Annual Research Report
  • [Journal Article] RNA interference of PPARγ using fiber-modified adenovirus vector efficiently suppresses preadipocyte-to-adipocyte differentiation in 3T3-L1 cells.2005

    • Author(s)
      Hosono T., Mizuguchi H., Watanabe Y., et al.
    • Journal Title

      Gene 348

      Pages: 157-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] RNA interference of PPARγ using fiber-modified adenovirus vector efficiently suppresses preadipocyte-to-adipocyte differentiation in 3T3-L1 cells.2005

    • Author(s)
      Hosono, T., Mizuguchi, H., Watanabe, Y, Hayakawa, T., et al.
    • Journal Title

      Gene 348

      Pages: 157-165

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] RNA interference of PPARgamma using fiber-modified adenovirus vector efficiently suppresses preadipocyte-to-adipocyte differentiation in 3T3-L1 cells.2005

    • Author(s)
      Hosono T., Watanabe T., et al.
    • Journal Title

      Gene 348

      Pages: 157-165

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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