الفهرس 
Pemphigus vulgarisOnly 14 pages are availabe for public view
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Abstract
Pemphigus vulgaris (PV) is a chronic autoimmune disease
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 mucosaldominant
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.
Other studies showed that normal proliferation and supporting
terminal epidermal differentiation further relies on activation of the
Notch-1 signaling pathways.
Notch activation typically requires cell–cell contact because
Notch-1 receptors & ligands are cell surface anchored molecules.
Studies showed that there is crosstalk between Notch-1
&cMYC as activation of the Notch signaling pathway results in
downregulation of cMYC which is needed for proper keratinocytes
proliferation and differentiationthrough the induction stem cell
differentiation during tissue regeneration and to prevent their
transformation.
Hence, in the current study we aimed at investigating the
expression of PG, cMYC and Notch-1expression in PV to evaluate the
probable effect of their expression in stem cell deregulation and how
could this participate in the disease pathogenesis.
This case-control study was carried out on 40 subjects. These
included 20 patients of PV and 20 age and sex matched normal
subjects. Patients were selected randomly from the Outpatient Dermatology Clinic, Menoufia University Hospital in the period
between June 2015 and June 2017. All patients were subjected to
history taking and complete general and dermatological examination.
A punch biopsy was taken from lesional and perilesional skin of all
PV patientsafter taking a written consent.