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Cells in non\u2010olfactory tissues tend to express more than one individual<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>gene, but function and interaction of two or more<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>s in the same cell type has only been marginally analysed. Here, we revealed<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>2A4\/7 and<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>51B5 as two new<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>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<jats:sup>2+<\/jats:sup>signals that are mediated by<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>2A4\/7 and<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\u2010dependent pathway. Localization studies and functional characterization of both receptors revealed several differences.<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>2A4\/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>and Chk\u20102 and secretion of<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101. In contrast,<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27,<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>1 and p38<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>phosphorylation and interestingly,<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 secretion. These findings underline that different<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>s perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.<\/jats:p>","DOI":"10.1111\/exd.13132","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T14:36:38Z","timestamp":1466174198000},"page":"58-65","source":"Crossref","is-referenced-by-count":98,"title":["Two olfactory receptors\u2014<scp>OR<\/scp>2A4\/7 and<scp>OR<\/scp>51B5\u2014differentially affect epidermal proliferation and differentiation"],"prefix":"10.1111","volume":"26","author":[{"given":"Teresa","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Cell Physiology Ruhr\u2010University Bochum Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Veitinger","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology 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