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  • 1
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Recent studies have reported nuclear delocalization of plakoglobin in acantholytic pemphigus vulgaris cells. The objective of this study was to evaluate the role of plakoglobin in the pathogenesis of acantholysis in pemphigus vulgaris (PV) and its relation with the urokinase-type plasminogen activator receptor (uPAR) expression.Materials and methods:  Plakoglobin and uPAR expressions were evaluated by immunohistochemistry in 22 cases of PV at various stages of the disease, and as controls in 18 specimens of skin/oral mucosa from healthy patients.Results:  Healthy skin/normal oral mucosa showed strong plakoglobin expression in the basal and spinous layers with prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of the epithelium. In PV patients, a progressive displacement of the plakoglobin signal toward the nucleus was found in 18/22 of the cases. Healthy skin/normal oral mucosa showed low uPAR expression with prevalent cellular membrane distribution. In the PV patients, strong uPAR expression was present in the acantholytic cells in 16/22 of the cases. There was direct correlation (p 〈 0.05) between the uPAR expression and nuclear plakoglobin.Conclusions:  The uPAR overexpression in acantholytic PV may be considered a direct consequence of plakoglobin abnormal distribution. Nuclear delocalization of plakoglobin, a direct consequence of plakoglobin-Dsg-3 dissociation induced by PV IgG, probably induces uPAR overexpression. This evidence suggests a central role for plakoglobin in PV pathogenesis because of its delocalization toward the nucleus, which is the probable cause of the uPAR gene expression.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of β- and γ-catenins in blistering diseases. The objective of this study was to evaluate the role of β- and γ-catenins in the pathogenesis of acantholysis in pemphigus vulgaris.Methods: β- and γ-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients.Results: Healthy skin and normal oral mucosa showed a strong β- and γ-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of γ-catenin was detected in 28/30 cases, and in 19/30 cases of PV for β-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for β-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for γ-catenin.Conclusions: Abnormal distribution of γ-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. γ-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the β-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.
    Type of Medium: Electronic Resource
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