Strict correlation between uPAR and plakoglobin expression in pemphigus vulgaris

Lorenzo Lo Muzio, Giuseppe Pannone, Stefania Staibano, Michele Davide Mignogna, Corrado Rubini, Giampietro Farronato, Francesca Ferrari, Pier Francesco Nocini, Gaetano De Rosa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)540-548
Number of pages9
JournalJournal of Cutaneous Pathology
Volume29
Issue number9
DOIs
Publication statusPublished - Oct 2002

ASJC Scopus subject areas

  • Dermatology
  • Pathology and Forensic Medicine

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