fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin

• Published in: Journal of cell science Vol. 123; no. 18; pp. 3102 - 3111
• Main Authors: Choi, Wonseon, Wolber, Rainer, Gerwat, Wolfram, Mann, Tobias, Batzer, Jan, Smuda, Christoph, Liu, Hongfang, Kolbe, Ludger, Hearing, Vincent J
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15.09.2010; Company of Biologists
• Subjects: Adult; Cells, Cultured; Fibroblasts - metabolism; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Melanocytes - metabolism; Neuregulin-1 - genetics; Neuregulin-1 - metabolism; Skin - metabolism; Skin Pigmentation
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.064774

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.