title: MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar.
abstract: 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.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Wound Healing Research Group, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Kwan
authors.affiliation: Wound Healing Research Group, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Wound Healing Research Group, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Division of Critical Care, Department of Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Tredget
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002056:Burns / Q000473:pathology; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000628:therapy*; D058575:Decorin / Q000096:biosynthesis*; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D009841:Oligonucleotides / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C546878:DCN protein, human; D058575:Decorin; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D053773:Transforming Growth Factor beta1
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