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

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.