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Abstract
Psoriasis vulgaris is a common skin disorder characterized by
focal formation of inflamed, raised plaques that constantly shed
scales derived from excessive growth of skin epithelial cells. The
disease is defined by a series of linked cellular changes in the skin:
hyperplasia of epidermal keratinocytes, vascular hyperplasia and
ectasia, and infiltration of T lymphocytes, neutrophils, and other types
of leucocytes in affected skin.
The cell cycle is an ordered set of events, culminating in cell
growth and division into two daughter cells. The stages of cell cycle
include; G1 stage which is the post-mitotic growth phase, the S stage
which is the stage when DNA replication occurs, the G2 stage which
is the pre-mitotic stage, and The M stage for mitosis
Cell-cycle progression is normally regulated by cyclins and
cyclin inhibiting proteins. Progression of cells from G 1 to S phase is
regulated via pRb phosphorylation by cyclin D complexed with CDK 4
and 6, which are in turn regulated by CDKI, such as p16 INK4
protein.
It was reported that the proliferate cell population is
approximately doubled in psoriasis, whereas the cell cycle is more
than 8 times shorter (36 versus 311 hours) and daily production of
keratinocytes in psoriatic lesions is approximately 28 times greater
than that in normal epidermis.
Summary
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These observation encouraged us to investigate the expression
of cyclin D1, as a positive regulator for cell cycle and the expression
of P16, as a negative regulator for the cell cycle, in lesional psoriatic
skin before and after receiving phototherapy and in normal skin in
order to detect a possible role of theses two parameters in the
pathogenesis of psoriasis.
The study was carried on Twenty five patients of
psoriasis (eleven male and fourteen female) and ten controls
of healthy individuals. Patients were either new cases that had
not received any treatment yet or recurrent cases who were
treated before by topical or systemic treatment. In these
recurrent cases, the last treatment stopped two months before
starting the phototherapy. Female patients who proved to be
pregnant were excluded from the study.
Skin biopsies were taken from affected skin of each
patient before starting and after twenty four sessions of
phototherapy and from controls to detect cyclin D1 and P16 in
them by reverse transcriptase (RT-PCR).
Statistical analysis of the results revealed the following:
· Value of cyclin D1 concentration in patients before
phototherapy was significantly higher than that of controls.
· Value of P16 concentration in patients before phototherapy was
significantly lower than that of controls.
Summary
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· There was statistically significant inverse correlation between
cyclin D1 and P16 in patients before therapy.
· Value of cyclin D1 in patients after 24 sessions of phototherapy
was significantly decreased than that before phototherapy.
· Value of P16 in patients after 24 sessions of phototherapy was
significantly increased than that before phototherapy.
· Following PUVA therapy, value of both cyclin D1 and P16
returned to normal levels.
· Following NB-UVB, value of P16 returned to normal levels;
however, value of cyclin D1 didn’t return to normal levels.
· There was no statistically significant difference, in the levels of
both cyclin D1 and P16, between patients who were treated
with UVB (narrow band) and those who were treated with
PUVA.
· There was no statistically significant correlation between both
cyclin D1 and P16 levels in patients before therapy and the
PASI score.
· There was no statistically significant correlation between both
cyclin D1 and P16 levels in patients before therapy and the
duration of the disease.
Summary
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These findings indicate that cyclin D1 is significantly
upregulated and P16 is significantly downregulated in
psoriasis and thus they could play a role in the pathogenesis
of psoriasis among other factors. In addition the significant
change in the levels of cyclin D1 and P16 after phototherapy
points that normalization of the level of these two
parameters could be one of the mechanisms by which UVR
treats psoriasis.
However, studying both parameters in other lines of
therapy not working on DNA could be helpful to detect
whether theses changes were primary or secondary to the
effect of UVR on DNA.