title: Reduced decorin, fibromodulin, and transforming growth factor-β3 in deep dermis leads to hypertrophic scarring.
abstract: Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-β1 and small leucine-rich proteoglycans (SLRPs) with fibroblast subtype and function may influence the development of HTS. The aim of this study was to characterize the expression and localization of factors that regulate wound healing including SLRPs, TGF-β1, and TGF-β3 in an experimental human SW and deep wound (DW) scar model including fibroblasts from superficial and deep layers of normal dermis. A 6-cm horizontal dermal scratch experimental wound was created, which consisted of progressively deeper wounds that were superficial at one end (0-0.75 mm deep) and deep (0.75-3 mm deep) at the other end, located on the anterior thigh of an adult male. Immunofluorescence staining, immunoblotting, reverse transcription polymerase chain reaction, and flow cytometry were performed to analyze the cellular and molecular differences between the SW scar and DW scar as well as fibroblasts isolated from superficial layer (L1) and deep layer (L5) of normal dermis. Comparing SWs and L1 fibroblasts, the expression of decorin, fibromodulin, and TGF-β3 was considerably lower than in DWs and L5 fibroblasts; however, TGF-β1 was higher in the deeper dermal wounds. When compared with L1 fibroblasts, L5 fibroblasts had lower Thy-1 immunoreactivity and significantly higher expression of TGF-β receptor type II. Decreased antifibrotic molecules in matrix of deep dermis of the skin and the unique features of the associated fibroblasts including an increased sensitivity to TGF-β1 stimulation contribute to the development of HTS after injuries involving the deep dermis.
authors.affiliation: Wound Healing Research Group, Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Alberta, Edmonton, Canada.
authors.forename: Dariush
authors.initials: D
authors.lastname: Honardoust
authors.forename: Mathew
authors.initials: M
authors.lastname: Varkey
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Marcoux
authors.forename: Heather A
authors.initials: HA
authors.lastname: Shankowsky
authors.forename: Edward E
authors.initials: EE
authors.lastname: Tredget
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D017439:Cicatrix, Hypertrophic / Q000209:etiology / Q000378:metabolism*; D058575:Decorin / Q000378:metabolism*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D000071235:Fibromodulin; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D009779:Occlusive Dressings; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000378:metabolism*; D013848:Thigh; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
chemical_list: D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D011509:Proteoglycans; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3; D000071235:Fibromodulin