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Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor‐intact or heterozygous skin
Author(s) -
Bautista RobertMarlo,
Carter Katharine Marie,
Jarrett Stuart Gordon,
Napier Dana,
Wakamatsu Kazumasa,
Ito Shosuke,
D'Orazio John August
Publication year - 2020
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12817
Subject(s) - melanocortin 1 receptor , melanin , skin cancer , melanocyte , biology , melanoma , pyrimidine dimer , human skin , phenotype , nucleotide excision repair , dna damage , forskolin , melanocortin , receptor , cancer research , endocrinology , genetics , dna , gene , cancer
Homozygous loss of function of the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity is less well studied, although individuals inheriting one loss‐of‐function MC1R allele are also melanoma‐prone. Using the K14‐Scf C57BL/6J animal model whose skin is characterized by lifelong retention of interfollicular epidermal melanocytes like that of the human, we studied pigmentary, UV responses, and DNA repair capacity in the skin of variant Mc1r background. Topical application of forskolin, a skin‐permeable pharmacologic activator of cAMP induction to mimic native Mc1r signaling, increased epidermal eumelanin levels, increased the capacity of Mc1r ‐heterozygous skin to resist UV‐mediated inflammation, and enhanced the skin's ability to clear UV photolesions from DNA. Interestingly, topical cAMP induction also promoted melanin accumulation, UV resistance, and accelerated clearance in Mc1r fully intact skin. Together, our findings suggest that heterozygous Mc1r loss is associated with an intermediately melanized and DNA repair‐proficient epidermal phenotype and that topical cAMP induction enhances UV resistance in Mc1r ‐heterozygous or Mc1r ‐wild‐type individuals by increasing eumelanin deposition and by improving nucleotide excision repair.