title: Insufficient expression of the melanocortin-1 receptor by human dermal fibroblasts contributes to excess collagen synthesis in keloid scars.
abstract: Activation of the α-melanocyte-stimulating hormone (αMSH)/melanocortin-1 receptor (MC1R) signalling pathway exerts antagonistic actions on cutaneous inflammatory and fibrogenic responses in addition to promoting pigment production. Herein, the expression of MC1R by keloid-derived fibroblasts and keloid scar tissue was investigated using a range of techniques. MC1R mRNA expression levels in five different keloid fibroblast cell lines were significantly reduced to less than half compared with five normal fibroblast cell lines (P < 0.05). Immunohistological analysis of tissue samples indicated that MCR1 immunoreactivity in both epidermal and dermal compartments of five keloid tissue samples was dramatically decreased compared with normal skin (P < 0.05). Insufficient expression of MC1R on human dermal fibroblasts might abolish the αMSH-mediated suppression of collagen production and myofibroblast transformation elicited by the profibrotic cytokine-transforming growth factor-β1. Restoration of reduced MC1R by dermal fibroblasts may lead to novel scar-reducing therapeutic approaches for treating this refractory fibrotic disease.
authors.affiliation: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Long-Fei
authors.initials: LF
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Shi-Zheng
authors.initials: SZ
authors.lastname: Xu
authors.forename: Tie-Chi
authors.initials: TC
authors.lastname: Lei
mesh_terms: D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007627:Keloid / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D044102:Receptor, Melanocortin, Type 1; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D000521:alpha-MSH; D003094:Collagen
keywords: MC1R; fibroblast; fibrogenesis; keloid; myofibroblast