The effects of dickkopf 1 on gene expression and wnt signaling by melanocytes: Mechanisms underlying its suppression of melanocyte function and proliferation

Yuji Yamaguchi, Thierry Passeron, Hidenori Watabe, Ken Ichi Yasumoto, Francois Rouzaud, Toshihiko Hoashi, Vincent J. Hearing

研究成果: Article査読

82 被引用数 (Scopus)

抄録

Dickkopf 1 (DKK1), which is expressed at high mRNA levels by fibroblasts in the dermis of human skin on the palms and soles, inhibits the function and proliferation of melanocytes in the epidermis of those areas via the suppression of β-catenin and microphthalmia-associated transcription factor (MITF). In this study, we investigated the protein expression levels of DKK1 between palmoplantar and non-palmoplantar areas and the effects of DKK1 on melanocyte gene expression profiles and on Wnt signaling pathways using DNA microarray technology, reverse transcriptase-PCR, Western blot, 3-dimensional reconstructed skin, immunocytochemistry, and immunohistochemistry. DKK1-responsive genes included those encoding proteins involved in the regulation of melanocyte development, growth, differentiation, and apoptosis (including Kremen 1, G-coupled receptor 51, lipoprotein receptor-related protein 6, low-density lipoprotein receptor, tumor necrosis factor receptor super-family 10, growth arrest and DNA-damage-inducible gene 45β, and MITF). Of special interest was the rapid decrease in expression of MITF in melanocytes treated with DKK1, which is concurrent with the decreased activities of β-catenin and of glucose-synthase kinase 3β via phosphorylation at Ser9 and with the upregulated expression of protein kinase Cα. These results further clarify the mechanism by which DKK1 suppresses melanocyte density and differentiation, and help explain why DKK1-rich palmoplantar epidermis is paler than non-palmoplantar epidermis via mesenchymal-epithelial interactions.

本文言語English
ページ(範囲)1217-1225
ページ数9
ジャーナルJournal of Investigative Dermatology
127
5
DOI
出版ステータスPublished - 2007 5月
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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