الفهرس 
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Abstract
Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease
characterized by development of autoantibodies against desmosomal cadherins
desmoglein (Dsg 3 &Dsg 1) that result in desmosomal disruption and subsequent
suprabasal acantholysis.
Pemphigus vulgaris is divided into two subgroups: the mucosal dominant type
due to anti Dsg3 antibodies; and the mucocutaneous type due to both anti Dsg
3& 1antibodies.
Despite the confirmed role of antidesmoglein antibodies in PV, the exact
molecular mechanism of the subsequent acantholysis remains unknown, with
three main models of PV pathogenesis that include direct inhibition of Dsg3 and
Dsg1 adhesive interactions, affection of intracellular signaling pathways that
downregulates desmosomal adhesion and finally disruption of desmosome
dynamics (assembly and disassembly).
Many studies indicated the role of different desmosomal proteins in PV
pathogenesis by being a part of signaling pathways and act on gene expression.
Of these proteins the armadillo protein plakoglobin (PG), which associates with
the cytoplasmic tail of Dsg3, is crucially involved.
The studies indicated that besides adhesion, PG is involved in cell cycle
regulation via the control of various signaling pathways as Wnt pathway and
gene expression as cMYC, which in turn influences the delicate balance of stem
cell recruitment, proliferation and terminal differentiation in keratinocytes.
cMYC which is known as proto-oncogene is needed for proliferation and
terminal differentiation of epidermal keratinocytes.It was demonstrated that cMYC plays a key role in driving the exit of stem cells into the epidermal
transient amplifying compartment and then, the transient amplifying cells require low cMYC levels to commit terminal differentiation
In PV, it was suggested that, PV antibodies that target Dsg3, act through
the depletion of nuclear PG. As a consequence, abrogation of PG-mediated
cMYC control, will result in disturbed proliferation and terminal differentiation
of epidermis that might be mediated throughdisturbed stem cell control.