Insufficient expression of the melanocortin-1 receptor by human dermal fibroblasts contributes to excess collagen synthesis in keloid scars

Activation of the -melanocyte-stimulating hormone (MSH)/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 MSH-mediated suppression of collagen production and myofibroblast transformation elicited by the profibrotic cytokine-transforming growth factor-1. Restoration of reduced MC1R by dermal fibroblasts may lead to novel scar-reducing therapeutic approaches for treating this refractory fibrotic disease.