| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Yumi GIFU UNIVERSITY School of Medicine, Assistant, 医学部, 助手 (90291393)
ICHIKI Yoshiro GIFU UNIVERSITY Univ.Hospital, Lecturer, 医学部・附属病院, 講師 (30223093)
TAKAGI Hajime GIFU UNIVERSITY School of Medicine, Associate Professor, 医学部, 助教授 (70226752)
山田 孝宏 岐阜大学, 医学部・附属病院, 助手 (50324306)
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| Research Abstract |
Pemphigus (P) is an autoimmune bullous disease caused by autoantibodies against desmosomal adhesion molecules, desmoglein 1 (Dsg1) for P foliaceus (PF) or Dsg3 for P vulgaris (PV). The mechanisms how the binding of these antibodies to Dsgs leads to cell-cell detachment are still unknown. Keratinocytes are thought to response to the extracellular signals to control cell-cell and cell-matrix junctions as other cells. In this respect, we have been focusing on the outside-in signaling caused by PV-IgG binding to Dsg3. Through this project, we have obtained the following results. We showed PV-IgG-dependent activation of protein kinase C (PKC) mediating the secretion of plasminogen activator (Arch Dermatol Res 135 : 1556-1557, 1999), expression of plasminogen activator receptor (J Invest Dermatol Symp Proc 4 : 137-144, 1999), PKC-independent phosphorylation of Dsg3 associated with its degradation and dissociation from plakoglobin (Eur J Immunol 29 : 2233-2240, 1999), and the formation of Dsg3-deficient desmosomes (J Invest Dermatol 112 : 67-71, 1999). Furthermore, we showed the formation of Dsg3 aggregation and half-desmosomes before desmosome formation and the binding of PV-IgG to these aggregations caused endocytosis of PV-IgG-Dsg3 immune complexes (Lab Invest 80 : 1583-1592, 2000). We also used clinically Dsg1, 3 ELISA to follow the clinical course of PV and PF (Eur J Dermatol 10 : 18-21, 2000).
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