Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation

Teresa Tsai1, Sophie Veitinger1, Irina Peek1

  • 1Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.

Insights

Human skin cells utilize olfactory receptors (ORs) like OR2A4/7 and OR51B5 for diverse functions. These receptors, activated by specific odorants, influence cell processes and signaling, offering new avenues for skin disease treatment and wound repair.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cell Biology

Background:

  • Olfactory receptors (ORs), part of the G-protein coupled receptor family, are found in human skin.
  • Multiple ORs can be expressed in non-olfactory cells, but their co-expression and distinct functions are poorly understood.

Purpose of the Study:

  • To identify novel olfactory receptors in human skin cells.
  • To investigate the functional roles and signaling pathways of identified ORs in keratinocytes and melanocytes.
  • To explore the potential therapeutic applications of ORs in skin conditions.

Main Methods:

  • Identification and characterization of OR2A4/7 and OR51B5 in human skin.
  • Stimulation of cultured human keratinocytes with identified odorants (cyclohexyl salicylate, isononyl alcohol).
  • Measurement of intracellular calcium (Ca2+) signals and cyclic adenosine monophosphate (cAMP) levels.
  • Receptor knockdown experiments to confirm mediation.
  • Immunohistochemistry for receptor localization.
  • Analysis of downstream signaling pathways (AKT, Chk-2, Hsp27, AMPK1, p38MAPK) and cytokine secretion (IL-1, IL-6).

Main Results:

  • OR2A4/7 and OR51B5 were identified as functional olfactory receptors in human skin cells.
  • Cyclohexyl salicylate and isononyl alcohol were confirmed as agonists, inducing Ca2+ signals and activating cAMP pathways.
  • OR2A4/7 influences keratinocyte cytokinesis, proliferation, AKT/Chk-2 phosphorylation, and IL-1 secretion, localized in suprabasal keratinocytes and basal melanocytes.
  • OR51B5 promotes keratinocyte migration and monolayer regeneration, affecting Hsp27/AMPK1/p38MAPK phosphorylation and IL-6 secretion, exclusively in suprabasal keratinocytes.

Conclusions:

  • Different olfactory receptors (ORs) mediate distinct functions within cutaneous cells.
  • OR2A4/7 and OR51B5 play unique roles in epidermal homeostasis, cell cycle regulation, and wound repair.
  • Targeting specific ORs presents a promising strategy for treating skin diseases and enhancing wound healing.

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