| Project/Area Number |
14370735
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Sciences (2004)
Hokkaido University (2002-2003) |
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Principal Investigator |
NOMIZU Motoyoshi Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Professor, 薬学部, 教授 (00311522)
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| 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)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| 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)
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| Keywords | basement membrane / laminin / integrin / syndecan / chitosan / peptide / 創傷治癒 |
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| 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.
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