Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris
Acantholysis/prevention & control
Caspases/antagonists & inhibitors
Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors/immunology/metabolism
Issue Date: 
John Wiley and Sons
Gil MP, Modol T, España A, López-Zabalza MJ. Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris. Exp Dermatol. 2012 Apr;21(4):254-9.
Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis and by autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cytoskeleton remodelling and formation and disassembly of cell adhesion structures. We have previously demonstrated that HER (human epidermal growth factor receptor related) isoforms, Src (Rous sarcoma) and mammalian target of rapamycin (mTOR), three molecules implicated in signalling processes, take part in suprabasal acantholysis and apoptosis induced by PV-IgG in a mouse model. Our aim was to investigate whether upregulation of FAK is implicated in the development of PV lesions. Herein, using a mouse model, PV-IgG administration showed an increased level of FAK phosphorylated on 397 and 925 tyrosine residues in the basal layer of epidermis. When mice were pretreated with a FAK inhibitor (FI), the acantholysis of the basal layer of epidermis was absent. More interestingly, we observed that phosphorylated FAK (Y397/925) decreased when HER isoforms, Src, mTOR and pan-caspases inhibitors were employed before PV-IgG administration. In addition, pretreatment with the FI before PV-IgG injection prevented the changes in both Bax and Bcl-2 expression and caspase-9 and caspase-3 activities induced by PV-IgG. Finally, FI reduced the expression of phosphorylated Src and mTOR in the basal cells of epidermis. In conclusion, our data reveal a novel role of phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinases

Files in This Item:
Exp Dermatol. 2012.254.pdf
225,9 kB
Adobe PDF

Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.