| Project/Area Number |
07407025
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | GIFU UNIVERSITY |
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Principal Investigator |
KITAJIMA Yasuo Gifu University, School of Medicine, Professor, 医学部, 教授 (70111797)
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| Co-Investigator(Kenkyū-buntansha) |
ESAKI Chikako Gifu University, Univ.Hospital, Assistant, 医学部附属病院, 助手 (70283306)
AOYAMA Yumi Gifu University, Univ.Hospital, Assistant, 医学部附属病院, 助手 (90291393)
SEISHIMA Mariko Gifu University, Univ.Hospital, Lecturer, 医学部附属病院, 講師 (00171314)
井上 稲子 岐阜大学, 医学部附属病院, 助手 (60262771)
長田 和子 岐阜大学, 医学部附属病院, 助手 (30252133)
中谷 明美 岐阜大学, 医学部附属病院, 助手 (80242725)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥32,300,000 (Direct Cost: ¥32,300,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥24,900,000 (Direct Cost: ¥24,900,000)
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| Keywords | Keratinocytes / Cell-cell junction / Cell-matrix junction / Desmosome / Hemidesmosome / Integrin / bullous diseases / Hyper keratosis / 細胞一基質間接着 |
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| Research Abstract |
Epidermal keratinocytes response to the extracellular signals leading to control cell-cell and cell-matrix junctional adhesions, so as to control normal keratinization. The purposes of this research project are to elucidate molecular mechanisms for the control of structures and functions cytoskeletons and adhesion molecules in terms of signal transduction, by studying autoimmune blistering diseases, congenital epidermolysis bullosa and keratinization disorders as a model system. This approach may provide us with a mutual benefits between basic aspects of cytoskeleton and cell junctions and clinical aspects of bullous and keratinizing disorders.
Until last year, we had made a certain progress in clarifying the molecular mechanisms for blister formation in Pemphigus vulgaris (PV), which is an autoimmune blistering skin disease characterized by autoantibodies to a specific desmosomal constituent, desmoglein (Dsg) 3. We showed an involvement of calcium- and protein kinase C (PKC)-mediated i
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ntracellular signaling which leads to plasminogen activator (muPA) secretion and muPA receptor expression in response to pemphigus vulgaris (PV)-IgG-binding (J Invest Dermatol 104 : 33-37,1995,105 : 482-487,1997). This year, we showed that involvement of PV-PLC in PV-IgG-induced Biphasic increase in diacylglycerol, which is supposed to cause activation of PKC (J Invest Dermatol 109 : 650-655,1997), and that PV-IgG binding alone induced the phosphorylation of Dsg 3 and plakoglobin (PG). Although Dsg3 and PG were coprecipitated by PV-IgG-immunoprecipitation when treated with normal IgG,PG was not coprecipitated with Dsg3 when stimuated with PV-IgG,suggesting that PV-IgG-binding to Dsg causes the dissociation of Dsg from PG.We propose that these aberrant signal transduction responses to PV-IgG,which lead to Dsg3 and PG phosphorylation and their dissociation, may impair the desmosomal integrity from the inside of the cell, while PV-IgG-induced PKC signaling, linked with uPA secretion and its receptor expression on the cell surface, may mediate to dissociate preexisting desmosomes from the outside of the cell (J Clin Invest revised submitted). We also showed that 180kDa bullous pemphigoid antigen (BPAG2) is phosphorylated with TPA and this phosphorylation is always associated with translocation of BPAG2 (230 kDa) from cytosol to plasma membrane (J Invest Dermatol revised submitted). Less
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