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Identification and characterization of tissue specific active sites in the laminins

Research Project

Project/Area Number 14370735
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo University of Pharmacy and Life Sciences (2004)
Hokkaido University (2002-2003)

Principal Investigator

NOMIZU Motoyoshi  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Professor, 薬学部, 教授 (00311522)

Co-Investigator(Kenkyū-buntansha) NISHI Norio  Hokkaido University, Graduate School of Engineering, Guest Professor, 大学院・工学研究科, 客員教授 (70001857)
UTANI Atsushi  Kyoto University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (10292707)
KADOYA Yuichi  Kitasato University, School of Medicine, Lecture, 医学部, 講師 (10185887)
YAMADA Junji  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Associate Professor, 薬学部, 助教授 (60200721)
TAKAGI Mitsuhiro  Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Assistant Professor, 薬学部, 助手 (90267493)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsbasement membrane / laminin / integrin / syndecan / chitosan / peptide / 創傷治癒
Research Abstract

Laminins, heterotrimers composed of α,β, and γ chains, are multifunctional glycoproteins present in basement membranes. Laminins are the most important component of basement membranes during basement membrane assembly in early development. Laminins are involved in various biological activities such as cell adhesion, migration, growth, differentiation, tumor metastasis, and angiogenesis. Fifteen laminin isoforms have been identified and are tissue- and/or developmental stage-specifically expressed. Integrins, dystroglycan, syndecans, and the other several cell surface molecules are cellular receptors for laminins. We prepared various recombinant proteins, comprising the G domains of laminin α1,α3 and α4 chains, and tested their cell attachment activity. Several recombinant proteins showed cell attachment and neurite outgrowth activities. We also synthesized more than 500 overlapping peptides covering the entire G domains and tested their cell attachment activity. More than 20 peptides promoted cell attachment and five peptides inhibited the biological activity mediated by the recombinant proteins. Some of the peptides were found to interact with integrins and syndecans. Additionally, some of the cyclic peptides enhanced the activity. These results suggest that the active sites are involved in the biological functions of the laminin α chain G domains. These active peptides may be useful for defining of the molecular mechanism of laminin-receptor interactions and laminin-mediated cellular signaling pathways. We conjugated the laminin active peptides onto a chitosan membrane. The active laminin peptide-conjugated chitosan membranes enhanced the biological activity and promoted cell adhesion in a cell-type specific manner. We also demonstrated that the peptide-chitosan membrane can deriver cells and is applicable for keratinocyte transferring to wound bed. The peptide-chitosan approach may be a powerful cell transplantation tool for various tissues and organs.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (30 results)

All 2005 2004 2003 Other

All Journal Article (18 results) Publications (12 results)

  • [Journal Article] Bifunctional peptides derived from homologuos loop regions in the laminin α chain LG4 modules interact with both α2β1 integrin and syndecan-2.2005

    • Author(s)
      Fumiharu Yokoyama ら
    • Journal Title

      Biochemistry 44

      Pages: 9581-9589

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional sites in the laminin alpha chains.2005

    • Author(s)
      Nobuharu Suzuki ら
    • Journal Title

      Connect. Tissue Res. 46

      Pages: 142-152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bifunctional peptides derived from homologuos loop regions in the laminin a chain LG4 modules interact with both α2β1 integrin and syndecan-2.2005

    • Author(s)
      Yokoyama, F., Suzuki, N., Kadoya, Y., Utani, A., Nakatsuka, H., Nishi, N., Haruki, M., Kleinman, H.K., Nomizu, M.
    • Journal Title

      Biochemistry 44

      Pages: 9581-9589

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional sites in the laminin alpha chains.2005

    • Author(s)
      Suzuki, N., Yokoyama, F., Nomizu, M.
    • Journal Title

      Connect., Tissue Res. 46

      Pages: 142-152

    • NAID

      10018086866

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multifunctional peptide fibrils for biomedical materials.2004

    • Author(s)
      Shingo Kasai ら
    • Journal Title

      Biopolymers 76

      Pages: 27-33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic peptides from the loop region of the laminin alpha4 chain LG4 module show enhanced biological activity over liner peptides.2004

    • Author(s)
      Fumiharu Yokoyama ら
    • Journal Title

      Biochemistry 43

      Pages: 13590-13597

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multifunctional peptide fibrils for biomedical materials.2004

    • Author(s)
      Kasai, S., Ohga, Y., Mochizuki, M., Nishi, N., Kadoya, Y., Nomizu, M.
    • Journal Title

      Biopolymers 76

      Pages: 27-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic peptides from the loop region of the laminin alpha4 chain LG4 module show enhanced biological activity over linear peptides.2004

    • Author(s)
      Yokoyama, F., Suzuki, N., Haruki, M., Nishi, N., Oishi, S., Fujii, N., Utani, A., Kleinman, H.K., Nomizu, M.
    • Journal Title

      Biochemistry 43

      Pages: 13590-13597

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclic peptides from the loop region of the laminin alpha4 chain LG4 module show enhanced biological activity over linear peptides.2004

    • Author(s)
      Fumiharu Yokoyamaら
    • Journal Title

      Biochemistry 43

      Pages: 13590-13597

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Active sites in the carboxyl-terminal region of the laminin alpha chain in Drosophila neuronal cell spreading.2004

    • Author(s)
      Yasumitsu Takagiら
    • Journal Title

      Arch.Insect.Biochem.Physiol. 56

      Pages: 162-169

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of an active site on the laminin α5 chain G-domain that binds to CD44 and inhibits malignancy.2004

    • Author(s)
      Suguru Hibinoら
    • Journal Title

      Cancer Res. 64

      Pages: 4810-4816

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of a fasciclin I-like protein with cell attachment activity from sea urchin (Strongylocentrotus intermedius) ovaries.2004

    • Author(s)
      Koji Satoら
    • Journal Title

      Arch.Biochem.Biophys. 424

      Pages: 1-10

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Multifunctional peptide fibrils for biomedical materials.2004

    • Author(s)
      Shingo Kasaiら
    • Journal Title

      Biopolymers 76

      Pages: 27-33

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Laminin-1 peptide-conjugated chitosan membranes as a novel approach for cell engineering.2003

    • Author(s)
      Mayumi Mochizuki ら
    • Journal Title

      FASEB J. 17

      Pages: 875-877

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Biological Activities of Homologous Loop Regions in the Laminin Alpha Chain G Domains.2003

    • Author(s)
      Nobuharu Suzuki ら
    • Journal Title

      J. Biol. Chem. 278

      Pages: 45697-45705

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Laminin-1 peptide-conjugated chitosan membranes as a novel approach for cell engineering.2003

    • Author(s)
      Mochizuki, M., Kadoya, Y., Wakabayashi, Y., Kato, K., Okazaki, I., Yamada, M., Sato, T., Sakairi, N., Nishi, N., Nomizu, M.
    • Journal Title

      FASEB J. 17

      Pages: 875-877

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Biological Activities of Homologous Loop Regions in the Laminin Alpha Chain G Domains.2003

    • Author(s)
      Suzuki, N., Nakatsuka, H., Mochizuki, M., Nishi, N., Kadoya, Y., Utani, A., Oishi, S., Fujii, N., Kleinman, H.K., Nomizu, M.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 45697-45705

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of heparin binding sites in the laminin α2 chain LG4-5 module

    • Author(s)
      Takashi Yoshimuraら
    • Journal Title

      Peptide Science 2004 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Publications] Atsushi Utani: "Laminin α3 chain LG4 module induces matrix metalloproteinase-1 (MMP-1) through MAPK signaling"J.Biol.Chem.. 278. 34483-34490 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nobuharu Suzuki: "Syndecan binding sites in the laminin α1 chain G domain"Biochemistry. 42. 12625-12633 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Lourdes Ponce: "Identification of a potent peptide antagonist to an active laminin-1 sequence that blocks angiogenesis and tumor growth"Cancer Res.. 63. 5060-5064 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuichi Kadoya: "Role for laminin-α5 chain LG4 module in epithelial branching morphogenesis"Dev.Biol.. 263. 153-164 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nobuharu Suzuki: "Biological Activities of Homologous Loop Regions in the Laminin α Chain G Domains"J.Biol.Chem.. 278. 45697-45705 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shingo Kasai: "Multifunctional peptide fibrils for biomedical materials"Biopolymers. 76. 27-33 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masayoshi Makino: "Identification of Cell Binding Sites in the Laminin α5 Chain G domain"Exp. Cell Res.. 277. 95-106 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kozue Kato: "Identification of neurite outgrowth promoting sites on the laminin α3 chain G domain"Biochemistry. 41. 10747-10753 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikuko Okazaki: "Identification of biologically active sequences in the laminin α4 chain G domain"J.Biol.Chem.. 277. 37070-37078 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masanori Yamada: "Ile-Lys-Val-Ala-Val (IKVAV)-containing laminin α1 chain peptides form amyloid-like fibrils"FEBS Letters. 530. 48-52 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mayumi Mochizuki: "Laminin-1 peptide-conjugated chitosan membranes as a novel approach for cell engineering"FASEB Journal. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Junko lnagaki: "An association o IgG anti-laminin-1 autoantibodies with endometriosis infertile patients"Human Reproduction. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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

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