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Regulation of endothelial cell behavior by dystroglycan in neovascularization

Research Project

Project/Area Number 11470028
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

KANOH Yumiko (2000)  Department of Structural Analysis, Senior Staff, 循環器形態部, 室長 (30214498)

眞崎 知生 (1999)  国立循環器病センター研究所, 所長 (60009991)

Co-Investigator(Kenkyū-buntansha) 狩野 由美子  国立循環器病センター研究所, 循環器形態部, 室長 (30214498)
藤原 敬己  国立循環器病センター研究所, 循環器形態部, 部長 (10190092)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2000: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1999: ¥8,900,000 (Direct Cost: ¥8,900,000)
KeywordsLaminin / Fibronectin / Endothelial cell / Dystroglycan / Integrin / Neovascularization / Cytoskeleton / ファイブロネクチ / 血管内皮細胞
Research Abstract

We investigated a role of dystroglycan in the control of endothelial cell behavior in angiogenetic processes. The binding between endothelial cells and laminin-10 and -11 was dependent on endothelial dystroglycan, and was inhibited by heparin sulfate. It is well known that endothelial cells undergo migration, proliferation and tube formation in angeogenesis. All of these processes was regulated by dystroglycan. Expression of dystroglycan by endothelilal cell was cell cycle-dependent. The expression level was very low in G0 phase, in contrast to the high level expression in G2/M and S phases. Thus, endothelial expression of dystroglycan is under dynamic regulation and the expressed dystroglycan is involved in the control of cell behaviors.
Histochemical analysis showed that expression of dystroglycan was barely detectable both in the arteries and veins in the normal tissues whereas it was expressed at a high level in newly synthesized blood vessels in cancer tissues. To explore dystroglycan-dependent intracellular signal transduction cascade, we searched for a binding protein which associated with the intracellular domain of dystroglycan, and identified MAGI-1 as a candidate interactor of dystroglycan. MAGI-1 has two WW-domains and five PDZ domains. MAGI-1 bound to dystrolgycan by its WW-domains. MAGI-1 also bound to beta catenin by its fifth PDZ domain. Binding between MAGI-1 and beta catenin inhibited beta catenin degradation, and activated beta catenin - TCF/LEF1 cascade. These results indicated the presence of a signaling cascade between dystroglycan and the beta ctenin/TCF/LEF1 system linked by MAGI-1.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H.Shimizu: "Adhesion of cultured bovine aortic endothelial cells to laminin-1 mediated by dystroglycan"J.Biol.Chem.. 274. 11995-12000 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Hosokawa: "Neuron specific expression of cationic amino acid transporter 3 in the adult rat brain"Brain.Res.. 838. 158-165 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kanoh: "Lateral zone of cell-cell adhesion as the major fluid shear stress related signal transduction site"Circulation Res.,. 86. 425-433 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Okamoto: "Cholesterol oxidation switches the internalization pathway of ensothelin receptor type A from caveolae to clathrin coated pit"J.Biol.Chem.. 275. 6439-6446 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kakutani: "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1"Proc.Natl.Acad Sci.USA. 97. 360-364 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Katoh: "Stress fiber organization regulated by MLCK and Rho-kinase in cultured human fibroblasts."Am.J.Physiol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Katoh: "Methods in Enzymology, vol.325, Regulators and effectors of small GTPases"Academic Press. 12 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shimizu et al.: "Adhesion of cultured bovine aortic endothelial cells to laminin-1 mediated by dystroglycan"J.Biol. Chem.. 274. 11995-12000 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Hosokawa et al.: "Neuron specific expression of cationic amino acid transporter 3 in the adult rat brain"Brian. Res.. 838. 158-165 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kanoh et al.: "Lateral zone of cell-cell adhesion as the major fluid shear stress related signal transduction site"Circulation Res. 86. 425-433 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Okamoto et al: "Cholesterol oxidation switches the internalization pathway of ensothelin receptor type A fromvaveolae to cleathin coated pit"J.Biol. Chem.. 275. 6439-6446 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kakutani et al: "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1"Proc. Natl. Acad. Sci., U.S.A.. 97. 360-364 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kakutani et al: "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipporoten receptor-1"Proc. Natl. Acad. Sci., U.S.A./ t97. 360. 360-364 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Katoh et al.: "Isolation and in vitro contraction of stress fibers. In : W.E.Balch, C.J.Der and A.Hall eds. Regulators and effectors of small GTPases Part D : Rho family"Methods in Enzymology. Academic Press. 325. 369-380 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Katoh et al.: "Stree fiber organization regulated by MLCK and Rho-kinase in cultured human fibroblasts"Am. J.Physiol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kanoh: "Lateral zone of cell-cell adhesion as the major fluid shear stress related signal transduction site"Circulation Res.,. 86. 425-433 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Katoh: "Stress fiber organization regulated by MLCK and Rho-kinase in cultured human fibroblasts"Am.J.Physiol.,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Katoh: "Methods in Enzymology vol.325 Regulators and effectors of small GTPases"Academic Press. 12 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H. Shimizu et al: "Adhesion of cultured bovine aortic endothelial cells to laminin-1 mediated by dystroglycan"J. Biol. Chem.. 27. 11995-12000 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Hosokawa et al: "Neuron-specific expression of cationic amino acid transporter 3 in the adult rat brain"Brain Res.. 838. 158-165 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] X-F. Zhang et al: "Pharmacological characterization of Ca2+ entry channels in endothelin-1-induced contraction of rat aorta using LOE908 and SK & F 96365"Br. J. Pharmacol.. 127. 1388-1398 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M. Kakutani et al: "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1"Proc. Natl. Acad. Sci. USA. 97. 360-364 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M. Chen et al: "Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits"Arterioscler. Thromb. Vasc. Biol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Okamoto et al: "Cholesterol oxidation switches the internalization pathway of endothelin receptor type A from caveolate to clathrin-coated pits in chinese hamster ovary cells"J. Biol. Chem.. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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

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