The δ-opioid receptor affects epidermal homeostasis via ERK-dependent inhibition of transcription factor POU2F3

Christine Neumann, Mei Bigliardi-Qi, Christian Widmann, Paul L. Bigliardi

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Neuropeptides and their receptors are present in human skin, and their importance for cutaneous homeostasis and during wound healing is increasingly appreciated. However, there is currently a lack of understanding of the molecular mechanisms by which their signaling modulates keratinocyte function. Here, we show that δ-opioid receptor (DOPr) activation inhibits proliferation of human keratinocytes, resulting in decreased epidermal thickness in an organotypic skin model. DOPr signaling markedly delayed induction of keratin intermediate filament (KRT10) during in vitro differentiation and abolished its induction in the organotypic skin model. This was accompanied by deregulation of involucrin (IVL), loricrin, and filaggrin. Analysis of the transcription factor POU2F3, which is involved in regulation of KRT10, IVL, and profilaggrin expression, revealed a DOPr-mediated extracellular signal-regulated kinase (ERK)-dependent downregulation of this factor. We propose that DOPr signaling specifically activates the ERK 1/2 mitogen-activated protein kinase pathway to regulate keratinocyte functions. Complementing our earlier studies in DOPr-deficient mice, these data suggest that DOPr activation in human keratinocytes profoundly influences epidermal morphogenesis and homeostasis.

Original languageEnglish (US)
Pages (from-to)471-480
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number2
DOIs
StatePublished - Feb 13 2015

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