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 language | English (US) |
|---|---|
| Pages (from-to) | 58-65 |
| Number of pages | 8 |
| Journal | Experimental Dermatology |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
| Externally published | Yes |
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Keywords
- ectopic expression
- HaCaT
- keratinocytes
- proliferation
- wound healing
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation
AU - Tsai, Teresa
AU - Veitinger, Sophie
AU - Peek, Irina
AU - Busse, Daniela
AU - Eckardt, Josephine
AU - Vladimirova, Dilyana
AU - Jovancevic, Nikolina
AU - Wojcik, Sebastian
AU - Gisselmann, Günter
AU - Altmüller, Janine
AU - Ständer, Sonja
AU - Luger, Thomas
AU - Paus, Ralf
AU - Cheret, Jeremy
AU - Hatt, Hanns
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - ectopic expression
KW - HaCaT
KW - keratinocytes
KW - proliferation
KW - wound healing
UR - http://www.scopus.com/inward/record.url?scp=85007107570&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007107570&partnerID=8YFLogxK
U2 - 10.1111/exd.13132
DO - 10.1111/exd.13132
M3 - Article
VL - 26
SP - 58
EP - 65
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 1
ER -