title: The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin.
abstract: Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. In this study, we tested the hypothesis that dermal fibroblasts regulate the constitutive skin color of individuals ranging from very light to very dark. We used microarray analysis to compare gene expression patterns in fibroblasts derived from lighter skin types compared to darker skin types, with a focus on secreted proteins. We identified a number of genes that differ dramatically in expression and, among the expressed proteins, neuregulin-1, which is secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting that it is one of the major factors determining human skin color.
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wonseon
authors.initials: W
authors.lastname: Choi
authors.forename: Rainer
authors.initials: R
authors.lastname: Wolber
authors.forename: Wolfram
authors.initials: W
authors.lastname: Gerwat
authors.forename: Tobias
authors.initials: T
authors.lastname: Mann
authors.forename: Jan
authors.initials: J
authors.lastname: Batzer
authors.forename: Christoph
authors.initials: C
authors.lastname: Smuda
authors.forename: Hongfang
authors.initials: H
authors.lastname: Liu
authors.forename: Ludger
authors.initials: L
authors.lastname: Kolbe
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012880:Skin Pigmentation
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D020890:Neuregulin-1