title: Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators.
abstract: BACKGROUND
  Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses.
  
  
  METHODS
  Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.
  
  
  RESULTS
  Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium.
  
  
  CONCLUSIONS
  Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Pornthep
authors.initials: P
authors.lastname: Sirimahachaiyakul
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Ravi F
authors.initials: RF
authors.lastname: Sood
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Muffley
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Max
authors.initials: M
authors.lastname: Seaton
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Lin
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Armaly
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hocking
authors.affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Gibran
mesh_terms: D001741:Black or African American; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000503:physiopathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D017495:Hyperpigmentation / Q000503:physiopathology*; D017496:Hypopigmentation / Q000503:physiopathology*; D015603:Keratinocytes / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012867:Skin / Q000293:injuries; D012880:Skin Pigmentation / Q000502:physiology*; D044465:White People; D014945:Wound Healing / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D008543:Melanins