2004 Fiscal Year Final Research Report Summary
Identification and characterization of tissue specific active sites in the laminins
| 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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| Keywords | basement membrane / laminin / integrin / syndecan / chitosan / peptide |
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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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Research Products
(12 results)
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[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.
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Journal Title
Biochemistry 44
Pages: 9581-9589
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Multifunctional peptide fibrils for biomedical materials.2004
Author(s)
Kasai, S., Ohga, Y., Mochizuki, M., Nishi, N., Kadoya, Y., Nomizu, M.
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Journal Title
Biopolymers 76
Pages: 27-33
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Biochemistry 43
Pages: 13590-13597
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
FASEB J. 17
Pages: 875-877
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
J.Biol.Chem. 278
Pages: 45697-45705
Description
「研究成果報告書概要(欧文)」より
