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From the Departments of Pathology*
and
Dermatology,
The University of Michigan
Medical School, Ann Arbor, Michigan
Type I and type III procollagen are reduced in photodamaged human
skin. This reduction could result from increased degradation by
metalloproteinases and/or from reduced procollagen synthesis. In the
present study, we investigated type I procollagen production in
photodamaged and sun-protected human skin. Skin samples from severely
sun-damaged forearm skin and matched sun-protected hip skin from the
same individuals were assessed for type I procollagen gene expression
by in situ hybridization and for type I procollagen
protein by immunostaining. Both mRNA and protein were reduced (
65
and 57%, respectively) in photodamaged forearm skin compared
to sun-protected hip skin. We next investigated whether reduced type I
procollagen production was because of inherently reduced capacity of
skin fibroblasts in severely photodamaged forearm skin to synthesize
procollagen, or whether contextual influences within
photodamaged skin act to down-regulate type I procollagen synthesis.
For these studies, fibroblasts from photodamaged skin and
matched sun-protected skin were established in culture. Equivalent
numbers of fibroblasts were isolated from the two skin sites.
Fibroblasts from the two sites had similar growth capacities and
produced virtually identical amounts of type I procollagen protein.
These findings indicate that the lack of type I procollagen synthesis
in sun-damaged skin is not because of irreversible damage to fibroblast
collagen-synthetic capacity. It follows, therefore,
that factors within the severely photodamaged skin may act in some
manner to inhibit procollagen production by cells that are inherently
capable of doing so. Interactions between fibroblasts and the
collagenous extracellular matrix regulate type I procollagen synthesis.
In sun-protected skin, collagen fibrils exist as a highly
organized matrix. Fibroblasts are found within the matrix, in
close apposition with collagen fibers. In photodamaged skin,
collagen fibrils are shortened, thinned, and
disorganized. The level of partially degraded collagen is 3.6-fold
greater in photodamaged skin than in sun-protected skin, and
some fibroblasts are surrounded by debris. To model this
situation, skin fibroblasts were cultured in
vitro on intact collagen or on collagen that had been partially
degraded by exposure to collagenolytic enzymes. Collagen that had been
partially degraded by exposure to collagenolytic enzymes from either
bacteria or human skin underwent contraction in the presence of dermal
fibroblasts, whereas intact collagen did not. Fibroblasts
cultured on collagen that had been exposed to either source of
collagenolytic enzyme demonstrated reduced proliferative capacity (22
and 17% reduction on collagen degraded by bacterial collagenase or
human skin collagenase, respectively) and synthesized less type
I procollagen (36 and 88% reduction, respectively, on
a per cell basis). Taken together, these findings indicate that
1) fibroblasts from photoaged and sun-protected skin are similar in
their capacities for growth and type I procollagen production; and 2)
the accumulation of partially degraded collagen observed in
photodamaged skin may inhibit, by an as yet unidentified
mechanism, type I procollagen synthesis.
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