Two olfactory receptors—<scp>OR</scp>2A4/7 and<scp>OR</scp>51B5—differentially affect epidermal proliferation and differentiation

Abstract

Abstract 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.