Hypertrophic
scarring is a frequent fibroproliferative complication following deep dermal
burns leading to impaired function and lifelong disfigurement.
Decorin reduces
fibrosis and induces regeneration in many tissues, and is significantly downregulated in
hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that
microRNAs in these fibroblasts downregulate
decorin and blocking them would increase
decorin and may prevent hypertrophic
scarring. Lower
decorin levels were found in
hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A
decorin 3' un-translated region reporter assay demonstrated
microRNA decreased
decorin in deep dermal fibroblasts, and
microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that
hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an
antagomiR, it was possible to increase
decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of
decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β1 induced
decorin downregulation and myofibroblast differentiation in
hypertrophic scar fibroblasts, suggesting a potential
therapy for
hypertrophic scar.