Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation.
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.
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Teresa
T
Tsai
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Sophie
S
Veitinger
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Irina
I
Peek
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Daniela
D
Busse
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Josephine
J
Eckardt
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Dilyana
D
Vladimirova
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Nikolina
N
Jovancevic
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Sebastian
S
Wojcik
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Günter
G
Gisselmann
Cologne Center for Genomics, University of Köln, Köln, Germany.
Janine
J
Altmüller
Department of Dermatology, Center for Chronic Pruritus, University Hospital Münster, Münster, Germany.
Sonja
S
Ständer
University Hospital Münster, Münster, Germany.
Thomas
T
Luger
Department of Dermatology, Laboratory for Hair Research and Regenerative Medicine, University Hospital of Münster, Münster, Germany.
Ralf
R
Paus
Department of Dermatology, Laboratory for Hair Research and Regenerative Medicine, University Hospital of Münster, Münster, Germany.
Jeremy
J
Cheret
Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
Hanns
H
Hatt
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007097:Imines / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D062326:Re-Epithelialization; D018035:Receptors, Odorant / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014162:Transfection
D002121:Calcium Channel Blockers; D054815:Cyclic Nucleotide-Gated Cation Channels; D005233:Fatty Alcohols; D007097:Imines; D007378:Interleukins; D018035:Receptors, Odorant; C017759:9-(tetrahydro-2-furyl)-adenine; C014925:RMI 12330A; D000242:Cyclic AMP; D004110:Diltiazem; D000225:Adenine; C553990:isononyl alcohol; D002118:Calcium
HaCaT; ectopic expression; keratinocytes; proliferation; wound healing