الفهرس 
RETINOIDSOnly 14 pages are availabe for public view
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Abstract
Oral isotretinoin in low doses is an effective treatment
for facial wrinkling, seemingly with less irritancy than
tretinoin . The mechanism of action is related to an increase
in the production of collagen.
Retinoids are also thought to act by inhibiting
metalloproteinases leading to decreased collagen destruction
especially collagen types I and III.
Matrix metalloproteinases (MMPs) are zinc dependant
endopeptidases, which degrades ECM, twenty five members
have been discovered till now. MMPs not only degrade the
structural components of the ECM in normal and diseased
tissues but also many of the growth factors, cytokines,
membrane bound precursors, cell adhesion molecules are
substrates for MMPs, in addition to cleavage or activation of
their zymogen forms.
MMPs are not continuously expressed and their
activity is regulated at three levels which are: a) gene
expression via cytokines, growth factors, b) proenzyme
activation and c) inhibition of the active enzyme by
endogenous inhibitors (TIMP-1, TIMP-2, TIMP-3, and
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TIMP-4). There is a tightly regulated balance between these
enzymes and their inhibitors.
MMP-1 is commonly known as collagenase or
collagenase-1. It is being referred to also as fibroblast
collagenase or interstitial collagenase. MMP-1 is the only
enzyme able to initiate breakdown of the interstitial
collagens; collagen type I, collagen type II, and collagen type
III .MMP-1 is produced by various types of cells in vitro and
in vivo and its expression has been associated with
inflammation, wound healing, and tumor invasion, growth,
and metastasis .
Isotretinoin has been reported to affect MMPs.
However, the various reports are contradictory, since there is
evidence suggesting that retinoids increase, reduce, or do not
affect MMPs.
This study was carried for assessment and studying
effect of isotretinoin treatment on MMP-1 protein expression
in skin.
All specimens that were taken after isotretinoin
treatment showed a significant increase in MMP- 1 protein
expression in both epidermis (in the cytoplasm of most of the
keratinocytes) and dermis (in the dermal matrix and the
cytoplasm of most fibroblasts). There was also significant
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increase in epidermal thickness, a significant decrease in
number of melanocytes , a significant increase in the
collagen fiber content in the papillary dermis and prominent
increase in oxytalan fibers in the papillary dermis in most
areas. This indicates regeneration of elastic fibers in most
areas of papillary dermis. Furthermore, there was a
significant positive correlation between MMP-1 protein
expression and collagen content in the papillary dermis.
The apparent paradox between increased MMP-1
activity which degrade ECM and increased collagen and
elastic fiber content may be difficult to interpret. One
possibility is that other MMP-1 may not be affected in the
same way and may be of more relevance in the collagen
balance. Moreover, quantitative measurement by
immunohistochemistry may not be an accurate reflection of
the functional activity of the enzyme. On the same basis,
altered structure of collagen (probably drug-induced) may
render it less susceptible to the destructive effect of MMP in
spite of increased levels of the latter in the skin.
Also, the increased MMP-1 expression may be an
event secondary to increased collagen production. Another
speculation may be related to the exact type of collagen
deposited. MMP-1 seems to be most active on type III
collagen more efficiently than type I or II collagen. MMP-1
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has not significant activity against type II and IV collagen,
while our study did not determine the exact type of collagen
deposition. Moreover, the effect may be dose dependent with
inhibition of MMP-1 to a minor degree and increased
collagen production to a higher degree.
Further studies should be done to determine the exact
role of isotretinoin on different types and functions of MMPs
and their inhibitors (TIMPs)