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Two olfactory receptors— OR 2A4/7 and OR 51B5—differentially affect epidermal proliferation and differentiation
Author(s) -
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
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13132
Subject(s) - microbiology and biotechnology , receptor , biology , keratinocyte , epidermis (zoology) , signal transduction , cell growth , cell culture , biochemistry , genetics , anatomy
Olfactory receptors ( OR s), 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 OR s in the same cell type has only been marginally analysed. Here, we revealed OR 2A4/7 and OR 51B5 as two new OR s in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca 2+ signals that are mediated by OR 2A4/7 and OR 51B5, 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. OR 2A4/7 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, OR 51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK 1 and p38 MAPK phosphorylation and interestingly, IL ‐6 secretion. These findings underline that different OR s perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.