A synthetic sandalwood odorant induces wound-healing processes in human keratinocytes via the olfactory receptor OR2AT4

Daniela Busse, Philipp Kudella, Nana Maria Grüning, Günter Gisselmann, Sonja Ständer, Thomas Luger, Frank Jacobsen, Lars Steinsträßer, Ralf Paus, Paraskevi Gkogkolou, Markus Böhm, Hanns Hatt, Heike Benecke

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88 Scopus citations

Abstract

As the outermost barrier of the body, the skin is exposed to multiple environmental factors, including temperature, humidity, mechanical stress, and chemical stimuli such as odorants that are often used in cosmetic articles. Keratinocytes, the major cell type of the epidermal layer, express a variety of different sensory receptors that enable them to react to various environmental stimuli and process information in the skin. Here we report the identification of a novel type of chemoreceptors in human keratinocytes, the olfactory receptors (ORs). We cloned and functionally expressed the cutaneous OR, OR2AT4, and identified Sandalore, a synthetic sandalwood odorant, as an agonist of this receptor. Sandalore induces strong Ca 2+ signals in cultured human keratinocytes, which are mediated by OR2AT4, as demonstrated by receptor knockdown experiments using RNA interference. The activation of OR2AT4 induces a cAMP-dependent pathway and phosphorylation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Moreover, the long-term stimulation of keratinocytes with Sandalore positively affected cell proliferation and migration, and regeneration of keratinocyte monolayers in an in vitro wound scratch assay. These findings combined with our studies on human skin organ cultures strongly indicate that the OR 2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes.

Original languageEnglish (US)
Pages (from-to)2823-2832
Number of pages10
JournalJournal of Investigative Dermatology
Volume134
Issue number11
DOIs
StatePublished - Nov 5 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Busse, D., Kudella, P., Grüning, N. M., Gisselmann, G., Ständer, S., Luger, T., Jacobsen, F., Steinsträßer, L., Paus, R., Gkogkolou, P., Böhm, M., Hatt, H., & Benecke, H. (2014). A synthetic sandalwood odorant induces wound-healing processes in human keratinocytes via the olfactory receptor OR2AT4. Journal of Investigative Dermatology, 134(11), 2823-2832. https://doi.org/10.1038/jid.2014.273