A pathophysiologic role for epidermal growth factor receptor in pemphigus acantholysis

Meryem Bektas, Puneet S. Jolly, Paula Berkowitz, Masayuki Amagai, David S. Rubenstein

Research output: Research - peer-reviewArticle

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Abstract

The pemphigus family of autoimmune bullous disorders is characterized by autoantibody binding to desmoglein 1 and/or 3 (dsg1/dsg3). In this study we show that EGF receptor (EGFR) is activated following pemphigus vulgaris (PV) IgG treatment of primary human keratinocytes and that EGFR activation is downstream of p38 mitogen-activated protein kinase (p38). Inhibition of EGFR blocked PV IgG-triggered dsg3 endocytosis, keratin intermediate filament retraction, and loss of cell-cell adhesion in vitro. Significantly, inhibiting EGFR prevented PV IgG-induced blister formation in the passive transfer mouse model of pemphigus. These data demonstrate cross-talk between dsg3 and EGFR, that this cross-talk is regulated by p38, and that EGFR is a potential therapeutic target for pemphigus. Small-molecule inhibitors and monoclonal antibodies directed against EGFR are currently used to treat several types of solid tumors. This study provides the experimental rationale for investigating the use of EGFR inhibitors in pemphigus.

LanguageEnglish (US)
Pages9447-9456
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number13
DOIs
StatePublished - Mar 29 2013

Fingerprint

Acantholysis
Pemphigus
Epidermal Growth Factor Receptor
Immunoglobulin G
p38 Mitogen-Activated Protein Kinases
Desmoglein 3
Desmoglein 1
Intermediate Filaments
Blister
Keratins
Endocytosis
Keratinocytes
Cell Adhesion
Autoantibodies
Monoclonal Antibodies
Neoplasms
Therapeutics
In Vitro Techniques
Cell adhesion
Tumors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

A pathophysiologic role for epidermal growth factor receptor in pemphigus acantholysis. / Bektas, Meryem; Jolly, Puneet S.; Berkowitz, Paula; Amagai, Masayuki; Rubenstein, David S.

In: Journal of Biological Chemistry, Vol. 288, No. 13, 29.03.2013, p. 9447-9456.

Research output: Research - peer-reviewArticle

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