Affiliation:
1. Department of Surgery Faculty of Medicine & Dentistry, University of Alberta Edmonton Alberta Canada
2. Department of Medical Oncology/Department of Mathematical and Statistical Sciences Faculty of Medicine and Dentistry, University of Alberta Edmonton Alberta Canada
Abstract
AbstractHypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down‐regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro‐fibrotic transforming growth factor‐beta 1 (TGF‐β1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon‐alpha 2b (IFN‐α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF‐β1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF‐β1 and IFN‐α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF‐β1 and/or IFN‐α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription‐quantitative polymerase chain reaction, immunofluorescence staining and enzyme‐linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF‐β1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN‐α2b showed the opposite effect. IFN‐α2b significantly inhibited TGF‐β1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF‐β1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN‐α2b is an important agent in reducing fibrotic outcomes.