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 journalArticlepeer-review

21 Scopus citations


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
Issue number2
StatePublished - Feb 13 2015

Bibliographical note

Funding Information:
We are grateful to Birgit Lane and the team from Institute of Medical Biology, A*STAR for their help and support, and Tommy Baumann, Ting Ting Seah, and Alicia Yap for their excellent technical assistance. These studies were supported by funding from Swiss National Science Foundation (SNSF) grant 31003A-116811 to MB-Qi and by a core grant from the Singapore Biomedical Research Council of the Singapore Agency for Science, Technology, and Research (A*STAR). We also thank Lucy Robinson of Insight Editing, London, for her assistance in revising the manuscript.

Publisher Copyright:
© 2015 The Society for Investigative Dermatology.


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