| Project/Area Number |
16390314
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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 |
Dermatology
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| Research Institution | GIFU UNIVERSITY |
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Principal Investigator |
KITAJIMA Yasuo Gifu University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (70111797)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKI Yoshiro Gifu University, Gradudate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (30223093)
AOYAMA Yumi Gifu University, Univ. Hospital, Assistant Professor, 医学附属病院, 講師 (90291393)
高木 肇 岐阜大学, 大学院・医学系研究科, 助教授 (70226752)
市橋 直樹 高山赤十字病院, 部長 (50283304)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | Keratinocytes / Cell-cell junction / Signal transduction / Desmosome / Pemphigus / Bullous diseases / Desmoglein / dissociation assay / 自己免疫性水疱症 / 先天性表皮水疱症 / 自己免疫水疱症 / 先天性水疱症 |
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| Research Abstract |
Pemphigus (P) is an autoimmune bullous disease caused by disruption of desmosomes due to autoantibodies against desmosomal adhesion molecules, desmoglein 3 (Dsg3) for P vulgaris (PV) or Dsg1 for P foliaceus (PF). It is yet unknown how blisters are induced after PV-IgG bound to desmogleins. The aim of this study is to elucidate the mechanisms of PV-IgG-induced blistering. We have previously shown that PV-IgG causes phosphorylation of Dsg3 followed by depletion of Dsg3 from desmosomes. However, since PV-IgG contains antibodies against other antigens than Dsg3, it is not yet determined whether Dsg3- depletion activity of PV-IgG is due to only anti-Dsg3 activity. In this study we determined that this is caused by anti-Dsg3 activity by using pathogenic and non-pathogenic monoclonal antibodies against Dsg3 in cultured keratinocytes. We also demonstrated that the depletion activity is proportional to the pathogenicity and exerts a decrease in the cell-cell adhesion strength as examined by pipetting dissociation assay. Besides, Epidemolysis bullosa simplex is caused by mutation of keratin 5 or 14, which are the major keratins in epidermal basal cells. We have found out a new type of EBS, caused by a new mutation (K5 : 1649delG) with a new phonotype showing circulated blistering lesions. We made transgenic mice with this mutation of K5 but resulting in no phenotype.
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