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

Exp Dermatol. 2013 Nov;22(11):764-6. doi: 10.1111/exd.12250.

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.

Keywords: MC1R; fibroblast; fibrogenesis; keloid; myofibroblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Collagen / biosynthesis*
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Humans
  • Keloid / metabolism*
  • Melanocytes / cytology
  • Receptor, Melanocortin, Type 1 / metabolism*
  • Signal Transduction
  • Skin / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing
  • alpha-MSH / metabolism

Substances

  • Receptor, Melanocortin, Type 1
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • alpha-MSH
  • Collagen