Two olfactory receptors— OR 2A4/7 and OR 51B5—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 individualORgene, but function and interaction of two or moreORs in the same cell type has only been marginally analysed. Here, we revealedOR2A4/7 andOR51B5 as two newORs 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 byOR2A4/7 andOR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces acAMP‐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 ofAKTand Chk‐2 and secretion ofIL‐1. In contrast,OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27,AMPK1 and p38MAPKphosphorylation and interestingly,IL‐6 secretion. These findings underline that differentORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.