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

Teresa Tsai, Sophie Veitinger, Irina Peek, Daniela Busse, Josephine Eckardt, Dilyana Vladimirova, Nikolina Jovancevic, Sebastian Wojcik, Günter Gisselmann, Janine Altmüller, Sonja Ständer, Thomas Luger, Ralf Paus, Jeremy Cheret, Hanns Hatt

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalExperimental Dermatology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Odorant Receptors
Keratinocytes
Skin
Phosphorylation
Tissue
Cytokinesis
Salicylates
Melanocytes
Cell proliferation
G-Protein-Coupled Receptors
Interleukin-1
Skin Diseases
Epidermis
Cell Movement
Regeneration
Monolayers
Interleukin-6
Repair
Genes
Chemical activation

Keywords

  • ectopic expression
  • HaCaT
  • keratinocytes
  • proliferation
  • wound healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Tsai, T., Veitinger, S., Peek, I., Busse, D., Eckardt, J., Vladimirova, D., ... Hatt, H. (2017). Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation. Experimental Dermatology, 26(1), 58-65. https://doi.org/10.1111/exd.13132

Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation. / Tsai, Teresa; Veitinger, Sophie; Peek, Irina; Busse, Daniela; Eckardt, Josephine; Vladimirova, Dilyana; Jovancevic, Nikolina; Wojcik, Sebastian; Gisselmann, Günter; Altmüller, Janine; Ständer, Sonja; Luger, Thomas; Paus, Ralf; Cheret, Jeremy; Hatt, Hanns.

In: Experimental Dermatology, Vol. 26, No. 1, 01.01.2017, p. 58-65.

Research output: Contribution to journalArticle

Tsai, T, Veitinger, S, Peek, I, Busse, D, Eckardt, J, Vladimirova, D, Jovancevic, N, Wojcik, S, Gisselmann, G, Altmüller, J, Ständer, S, Luger, T, Paus, R, Cheret, J & Hatt, H 2017, 'Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation', Experimental Dermatology, vol. 26, no. 1, pp. 58-65. https://doi.org/10.1111/exd.13132
Tsai, Teresa ; Veitinger, Sophie ; Peek, Irina ; Busse, Daniela ; Eckardt, Josephine ; Vladimirova, Dilyana ; Jovancevic, Nikolina ; Wojcik, Sebastian ; Gisselmann, Günter ; Altmüller, Janine ; Ständer, Sonja ; Luger, Thomas ; Paus, Ralf ; Cheret, Jeremy ; Hatt, Hanns. / Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation. In: Experimental Dermatology. 2017 ; Vol. 26, No. 1. pp. 58-65.
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AU - Eckardt, Josephine

AU - Vladimirova, Dilyana

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