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

Christine Neumann1, Mei Bigliardi-Qi2, Christian Widmann3

  • 1Experimental Dermatology Laboratory, Institute of Medical Biology, A*STAR, Singapore; Doctoral School Faculty of Biology and Medicine, University of Lausanne, Dorigny, Switzerland; These authors contributed equally to this work.

Insights

Activation of the delta-opioid receptor (DOPr) in human skin inhibits keratinocyte proliferation and differentiation, impacting epidermal thickness. This signaling pathway involves the ERK pathway and affects key epidermal proteins.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • Neuropeptides and receptors are vital for skin homeostasis and wound healing.
  • Mechanisms linking neuropeptide signaling to keratinocyte function are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms of delta-opioid receptor (DOPr) signaling in human keratinocytes.
  • To investigate the impact of DOPr activation on epidermal development and homeostasis.

Main Methods:

  • Organotypic skin models were used to study keratinocyte proliferation and differentiation.
  • Analysis included keratin intermediate filament (KRT10), involucrin (IVL), loricrin, and filaggrin expression.
  • Investigated the role of the transcription factor POU2F3 and the ERK pathway.

Main Results:

  • DOPr activation inhibited human keratinocyte proliferation, reducing epidermal thickness.
  • Delayed KRT10 induction and disrupted IVL, loricrin, and filaggrin expression were observed.
  • DOPr signaling led to ERK-dependent downregulation of the transcription factor POU2F3.

Conclusions:

  • DOPr signaling, via the ERK pathway, regulates keratinocyte function and epidermal morphogenesis.
  • DOPr activation significantly influences human epidermal homeostasis.
  • Findings complement studies in DOPr-deficient mice, highlighting the receptor's role in skin.

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