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.