| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Takeji Keio University, Dermatology, Professor, 医学部, 教授 (50051579)
MIYASATO Minoru Kurume Univ., Dermatology, Ass. Prof., 医学部, 講師 (50182001)
MORI Osamu Kurume Univ., Dermatology, Associate Prof., 医学部, 助教授 (10175630)
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| Research Abstract |
In order to elucidate the role of different domains of desmoyokin (or AHNAK protein), we have prepared eukaryotic expression vectors (pcDNA/Amp1) of 3 different domains of desmoyokin, and transfected into COS7 cell, MDCK cells, KU8 cell, and normal keratinocytes. The results indicated that, although the N-terminal and central domains of desmoyokin are present in only cytoplasm, the C-terminal domain is responsible for the translocation to both nucleus and cell membrane. This indicates that desmoyokin may play an important role in both cell adhesion and intracellular signal transduction in keratinocytes.
In addition, using various biochemical techniques, we have shown for the first time that envoplakin and periplakin, newly identified cornified envelope proteins associated with desmosomes, are target antigens for paraneoplastic pemphigus, a recently identified disease entity of pemphigus group associated with hematological malignant tumors. These proteins are considered to Play an important role in both cell adhesion and differentiation in keratinocytes, and we will examine the role of these proteins in various inflammatory and skin diseases in the next project.
Furthermore, we have also shown that various desmosomal proteins are autoantigens for various autoimmune bullous diseases. Desmoglein 1 and 3 are detected as autoantigens in various autoimmune skin diseases, particularly herpetiform pemphigus and paraneoplastic pemphigus. We have also shown that desmocollin 1 is a target antigen for subcorneal pustular dermatosis type of IgA pemphigus. This study indicates for the first time that desmocollin can also be autoantigen for some skin diseases. This result also indicates that desmocollin may be involved not only in cell adhesion but also in various inflammation, such as leukocyte chemotaxis, because marked pustule formation is seen in subcorneal pustular dermatosis type of IgA pemphigus.
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