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2005 Fiscal Year Final Research Report Summary

Regulation of glycosmainoglycan chain formation in proteoglycan molecules synthesized by brain vascular cells

Research Project

Project/Area Number 16590070
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHokuriku University

Principal Investigator

KAJI Toshiyuki  Hokuriku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90204388)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Chika  Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (70230571)
FUJIWARA Yasuyuki  Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40247482)
Project Period (FY) 2004 – 2005
KeywordsVascular / Endothelial cell / Pericyte / Proteoglycan / Glycosaminoglycan / Heparan sulfate / Chondroitin sulfate / Dermatan sulfate
Research Abstract

A member of the vascular endothelial growth factor (VEGF) family, VEGF165 regulates vascular endothelial cell functions in autocrine and paracrine fashions in microvessels. Proteoglycans are highly glycosylated poly-anionic macromolecules that influence cellular behaviors such as proliferation and migration by interacting with cytokines/growth factors. In the present study, we investigated the regulation of proteoglycan synthesis by VEGF165 in cultured human brain microvascular endothelial cells. The cells were exposed to recombinant human VEGF165, and the proteoglycans were then characterized using biochemical techniques. VEGF165 treatment increased the accumulation of proteoglycans 1.4- and 1.6-fold in the cell layer and conditioned medium, respectively. This effect resulted from the activation of VEGFR2, and was mimicked by vammin, a VEGFR2 ligand from snake venom but not placenta growth factor, which binds specifically to VEGFRI. VEGF165 stimulated the production and secretion of perlecan, substituted with shorter heparan sulfate side chains, but with unaltered sulfated disaccharide composition. The perlecan secreted by VEGF 165 -stimulated endothelial cells may be involved in the regulation of cellular behavior during angiogenesis, in diseases of the brain microvessels, and in the maintenance of the endothelial cell monolayer.

  • Research Products

    (10 results)

All 2006 2005 2004

All Journal Article (10 results)

  • [Journal Article] Identification and functions of chondroitin sulfate in the milieu of neural stem cells2006

    • Author(s)
      Ida M et al.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 5982-5991

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification and functions of chondroitin sulfate in the milieu of neural stem cells.2006

    • Author(s)
      Ida, M., Shuo, T., Hirano, K., Tokita, Y., Nakanishi, K., Matsui, F., Aono, S., Fujita, H., Fujiwara, Y., Kaji, T., Oohira, A.
    • Journal Title

      J.Biol.Chem. 281

      Pages: 5982-5991

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Proteoglycans predominantly synthesized by human brain microvascular endothelial cells in culture are perlecan and biglycan2005

    • Author(s)
      Yamamoto C et al.
    • Journal Title

      J. Health Sci. 51

      Pages: 576-583

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of synthesis of a large heparan sulfate proteoglycan, perlecan. by thrombin in cultured human coronary smooth muscle cells2005

    • Author(s)
      Yamamoto C et al.
    • Journal Title

      Biochim. Biophys. Acta 1722

      Pages: 92-102

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Proteoglycans predominantly synthesized by human brain microvascular endothelial cells in culture are perlecan and biglycan.2005

    • Author(s)
      Yamamoto, C., Deng, X., Fujiwara, Y., Kaji, T.
    • Journal Title

      J.Health Sci. 51

      Pages: 576-583

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction of synthesis of a large heparan sulfate proteoglycan, perlecan, by thrombin in cultured human coronary smooth muscle cells.2005

    • Author(s)
      Yamamoto, C., Wakata, T., Fujiwara, Y., Kaji, T.
    • Journal Title

      Biochim.Biophys.Acta 1722

      Pages: 92-102

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of chondroitin/dermatan sulfate proteoglycans synthesized by bovine retinal pericytes in culture2004

    • Author(s)
      Kaji T et al.
    • Journal Title

      Biol. Pharm. Bull 27

      Pages: 1763-1768

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential regulation of biglycan and decorin synthesis by connective tissue growth factor in cultured vascular endothelial cells2004

    • Author(s)
      Kaji T et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 322

      Pages: 22-28

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of chondroitin/dermatan sulfate proteoglycans synthesized by bovine retinal pericytes in culture.2004

    • Author(s)
      Kaji, T., Sakurai, S., Yamamoto, C., Fujiwara, Y., Yamagishi, S., Yamamoto, H., Kinsella, M.G., Wight, T.N.
    • Journal Title

      Biol.Pharm.Bull. (Highlighted paper selected by Editor in-chief) 27

      Pages: 1763-1768

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential regulation of biglycan and decorin synthesis by connective tissue growth factor in cultured vascular endothelial cells.2004

    • Author(s)
      Kaji, T., Yamamoto, C., Oh-i, M., Nishida, T., Takigawa, M.
    • Journal Title

      Biochem.Biophys.Res.Commun. 322

      Pages: 22-28

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

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Published: 2007-12-13  

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