Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation
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Updated: Mar 19, 2026

Live-cell Measurement of Odorant Receptor Activation Using a Real-time cAMP Assay
Published on: October 2, 2017
Teresa Tsai1, Sophie Veitinger1, Irina Peek1
1Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Abstract:
Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca2+ signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.
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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