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ROLE OF ENDOTHELIAL CELL, PERICYTE, AND ASTROCYTE ON BASEMENT MEMBRANE METABOLISM IN BLOOD-TISSUE BARRIER

Research Project

Project/Area Number 16590120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKyoritsu University of Pharmacy

Principal Investigator

NAKASHIMA Emi  KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACEUTICS, PROFESSOR, 薬学部, 教授 (90115254)

Co-Investigator(Kenkyū-buntansha) SAI Yoshimichi  KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACEUTICS, ASSOCIATE PROFESSOR, 薬学部, 助教授 (40262589)
KOSE Noriko  KYORITSU UNIVERSITY OF PHARMACY, DEPARTMENT OF PHARMACEUTICS, ASSISTANT PROFESSOR, 薬学部, 助手 (60348612)
飯笹 久  共立薬科大学, 薬学部, 助手 (80306662)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsblood-brain barrier / basement membrane / endothelial cell / pericyte / astrocyte / endothelial progenitor cell / smooth muscle cell / conditionally immortalized cell line / 血管脳関門 / 細胞分化 / 管腔形成 / タイトジャンクション / SV40 T抗原
Research Abstract

The basement membrane at the blood-brain barrier (BBB) plays important roles in maintaining the structure and function of capillary vessels. The BBB is constructed from endothelial cells, astrocytes and pericytes, but their inter-relationships in formation or maintenance of basement membrane are poorly understood. Previously, we established the conditionally immortalized cell lines of brain capillary pericyte (TR-PCT), bone marrow endothelial progenitor cell derived cell (TR-BME) from the transgenic rats with a temperature sensitivity SV40 T antigene gene. It was found that the mRNA level of α-smooth muscle actin in a brain capillary pericyte cell line TR-PCT1 was increased by treatment with TGF-β1. TR-PCTs retained biological activity of the calcification to matrix by the b-glycerophosphate.
In this study, the expression of mRNAs encoding basement membrane-related molecules in TR-PCT1, a rat endothelial cell line TR-BBB13, and a type 2 astrocyte cell line TR-AST4 was evaluated by RT-PCR analysis. The effects of TGF-β1 on expression of basement membrane-related genes in these cell lines were also examined. In order to identify the role of endothelial progenitor cells on barrier function, we compared the specific genes by means of subtractive hybridization between TR-BBB and TR-BME cells.
Collagen type IV is the main constituent, and produced mainly by astrocyte. TR-PCT produce fibronectine, about 5 times higher than that of endothelial cell. TR-PCT showed high expressions of MMP-9 and tPA, the decomposition component of basement membrane. Thus, we showed that pericyte is highly active and may be a key cell which control the regulation of basement membrane. TR-BME cells have higher levels of smooth muscle cell(SMC) markers compared with mature endothelial cell, and can differentiate into contractile- or synthetic-type SMC.
These results suggest that pericytes and progenitor cells may be key cells in the maintenance of basement membrane and its function.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] Mechanical analysis of tumor growth regression by the cyclooxygenase-2 inhibitor, DFU, in a walker256 rat tumor model : Inportance of monocyte chemoattractant protein-1 modulation.2006

    • Author(s)
      Muta M, Matsumoto G, Nakashima E, Toi M.
    • Journal Title

      Clin Cancer Res 12(1)

      Pages: 264-272

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Platelet-derived growth factor-BB (PDGF-BB) induces differentiation of bone marrow endothelial progenitor cell-derived cell line TR-BME2 into mural cells and changes the phenotype.2005

    • Author(s)
      Miyata T, Iizasa H, Sai Y, Fujii J, Terasaki T, Nakashima E
    • Journal Title

      J Cell Physiol 204(3)

      Pages: 948-955

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prediction of theophylline clearance in CCl4-treated rats using in vivo CYP1A2 and CYP3A2 contents assessed with the PKCYP test.2005

    • Author(s)
      Kose N, Yamamoto K, Sai Y, Isawa M, Suwa T, Nakashima E
    • Journal Title

      Drug Metab Pharmacokinet 20(3)

      Pages: 168-176

    • NAID

      130004462958

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Platelet-derived growth factor-BB (PDGF-BB) induces differentiation of bone marrow endothelial progenitor cell-derived cell line TR-BME2 into mural cells, and changes the phenotype.2005

    • Author(s)
      Miyata T, Iizasa H, Sai Y, Fujii J, Terasaki T, Nakashima E.
    • Journal Title

      J Cell Physiol 204(3)

      Pages: 948-955

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prediction of theophylline clearance in CC14-treated rats using in vivo CYP1A2 and CYP3A2 contents assessed with the PKCYP test.2005

    • Author(s)
      Kose N, Yamamoto K, Sai Y, Isawa M, Suwa T, Nakashima E.
    • Journal Title

      Drug Metab Pharmacokinet 20(3)

      Pages: 168-176

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Platelet-derived dgrowth factor-BB (PDGF-BB) induces differentiation of bone marrow endothelial progenitor cell-derived cell line TR-BME2 into mural cells, and changes the phenotype.2005

    • Author(s)
      Miyata T, Iizasa H, Sai Y, Fujii J, Terasaki T, Nakashima E.
    • Journal Title

      J Cell Physiol 204(3)

      Pages: 948-955

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Conditionally immortalized syncytiotrophoblast cell lines as new tools for study of the blood-placenta barrier.2004

    • Author(s)
      Kitano T, Iizasa H, Hwang IW, Hirose Y, Morita T, Maeda T, Nakashima E
    • Journal Title

      Biol Pharm Bull 27(6)

      Pages: 753-759

    • NAID

      110003608848

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Conditionally immortalized syncytiotrophoblast cell lines as new tools for study of the blood-placenta barrier.2004

    • Author(s)
      Kitano T, Iizasa H, Hwang IW, Hirose Y, Morita T, Maeda T, Nakashima E.
    • Journal Title

      Biol Pharm Bull 27(6)

      Pages: 753-759

    • NAID

      110003608848

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro.2004

    • Author(s)
      Hori S, Ohtsuki S, Hosoya K, Nakashima E, Terasaki T.
    • Journal Title

      J.Neuroshem. 89(2)

      Pages: 503-513

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Conditionally immortalized syncytiotrophoblast cell lines as new tools for study of the blood-placenta barrier.2004

    • Author(s)
      Kitano T, Iizasa H, Hwang IW, Hirose Y, Morita T, Maeda T, Nakashima F.
    • Journal Title

      Biol.Pharm.Bull. 27(6)

      Pages: 753-759

    • NAID

      110003608848

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhacement by asteocyte-derived soluble factor(s).2004

    • Author(s)
      Hori S, Ohtsuki S, Tachikawa M, Kimura N, Kondo T, Watanabe M, Nakashima E, Terasaki T.
    • Journal Title

      J.Neurochem. 90(3)

      Pages: 526-536

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo trafficking of endothelial progenitor cells and their possible involvement in tumor neovascularization.2004

    • Author(s)
      Tamura M, Unno K, Yonezawa S, Hattri K, Nakashima E, Tsukada H, Nakajima M, Oku N.
    • Journal Title

      Life Sci. 75(5)

      Pages: 575-584

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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