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Development of novel strategy for targeting of functional proteins into hasement membrance

Research Project

Project/Area Number 14580819
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionOsaka Univ.

Principal Investigator

SHASLIANG Li  Osaka Univ., Institute for protein research, Assistant professor, 蛋白質研究所, 助手 (40252720)

Co-Investigator(Kenkyū-buntansha) SEKIGUCHI Kiyotoshi  Osaka Univ., Institute for protein Research, Professor, 蛋白質研究所, 教授 (50187845)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsBasement membrane / lawiain / HGF / bFGF / VEGF / ターゲティング
Research Abstract

Growth factors bind to various ECM proteins including HSPG, collagen, and fibronectin. However, interaction with LN isoforms remains unknown. In this study, we examined the interaction of three angiogenesis-related growth factors, HGF, bFGF, and VEGF, with LN 1, 2/4, 5, 8, and 10/11 by ELISA. HGF bound preferentially to LN 10/11 and LN 8, and binding was inhibited by heparin, low pH, and heparitinase II treatment. Binding to the 293F cell-expressed LN 10 was weaker than that to LN 10/11 from A549 cells. Mutagenesis studies indicated that HGF-binding sites possibly reside in the short arm of LN 10. Moreover, LN 10/11-bound HGF promoted proliferation of HMEC-1 cells. bFGF also exhibited similar binding preference for LNs, and binding of VEGE to LNs is comparably weak. In conclusion, LN 10/11, rich in blood vessel basement membrane, could capture the angiogenesis-related growth factor such as HGF, bFGF and VEGF with different affinity to promote cell proliferation. These interactions were possibly regulated by such environment factors as heparan sulfate modification and pH change during different physiological or pathological processes.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Shigeta, M 他: "CD151 regulates epithelial cell-cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization"J.Cell Biol.. 163. 165-176 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiwara, H 他: "Rac regulates integrin-mediated endothelial cell adhesion and migration on laminin-8"Exp.Cell Res.. 292. 67-77 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeta M et al.: "CD151 regulates epiffetial cell-cell adhesion throagh PKC-and Cdc42-dependent actin cytoskeletal reorganization"J. cell Biol. 163. 165-176 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiwara H et al.: "Rac regulates integrin-mediated endothelial cell adiesion and aigration on lawiaia-8"Eep. cell Res. 292. 67-77 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shigeta, M. 他: "CD151 regulates epithelial cell-cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization"J.Cell Biol.. 163. 165-176 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Niimi, T. 他: "Identification of an upstream enhancer in the mouse laminin α1 gene defining its high level of expression in parietal endoderm cells"J.Biol.Chem.. 278. 9332-9338 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kozaki, T. 他: "Recombinant expression and characterization of a novel fibronectin isoform expressed in cartilaginous tissues"J.Biol.Chem.. 278. 50546-50553 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Futaki, S. 他: "Molecular basis of constitutive production of basement membrane components : Gene expression profiles of Engelbreth-Holm-Swarm tumor and F9 embryonal carcinoma cells"J.Biol.Chem.. 278. 50691-50701 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishiuchi, R. 他: "Characterization of ligand binding specificities of integrin α3β1 and α6β1 using a panel of purified laminin isoforms containing distinct αchains"J.Biochem.. 134. 497-504 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujiwara, H. 他: "Rac regulates integrin-mediated endothelial cell adhesion and migration on laminin-8"Exp.Cell Res.. 292. 67-77 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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