| Project/Area Number |
18591258
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Keio University |
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Principal Investigator |
ISHIKO Akira Keio University, School of Medicine, Associate Professor (10202988)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Yoshifumi Keio University, School of Medicine, Instructor (10306772)
AMAGAI Masayuki Keio University, School of Medicine, Professor (90212563)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | pemphigus / electron microscopy / cell adhesion / desmoglein / immunoelectron microscopy / desmosome / acantholysis / bullous disease / 病理学 / デスモソース |
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| Research Abstract |
Pemphigus is an autoimmune blistering disease caused by autoantibodies against desmoglein 1 and/ or desmoglein 3. The purpose of this study is to elucidate the mechanism whereby autoantibody binding lead to the blister formation using immunoelectron microscopy.
In the first year, we have collected more than 10 cases of pemphigus vulgaris and foliaceus (PF) and characterized their ultrastructural findings according to the clinical subtypes. As results, split of desmosomes and keratin retraction were the shared common features among all types of pemphigus. Split of desmosomes was the initial change of acantholysis and keratin retraction followed resulting in cell separation.
In the next year, we tried to immunolocalize the PF autoantibody binding site in the normal human epidermis, but it was unsuccessful. We are currently trying the other method for immunoelectron microscopy. We also tried to characterize PF in dogs. Canine PF can be an animal model of human PF and is worth elucidating. We have succeeded in identifying the ultrastructural binding site of the canine PF autoantibody binding site. It' was distributed around desmosome complex, both intra- and extracellularly by postembedding immunogold EM. By double staining with desmoplakin antibody, intracellular labeling of the PF serum co-localized with desmoplakin. By immunoblot analysis, a band with similar molecular weight to desmoplakin was detected using the canine PH serum. In addition, extracellular labeling of the serum co-localized with human PF antibody binding site, although immunoblotting was negative with human desmoglein 1. These results suggested that Canine PF autoantibody recognized desmosomal molecules including desmoplakin and unknown transmembrane molecule other than desmoglein 1.
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