期刊
EXPERIMENTAL DERMATOLOGY
卷 26, 期 1, 页码 58-65出版社
WILEY
DOI: 10.1111/exd.13132
关键词
ectopic expression; HaCaT; keratinocytes; proliferation; wound healing
类别
资金
- Common Fund of the Office of the Director of the National Institutes of Health
- NCI
- NHGRI
- NHLBI
- NIDA
- NIMH
- NINDS
- NCI/SAIC-Frederick, Inc. (SAIC-F) [10XS170, 10XS171, X10S172]
- Laboratory, Data Analysis and Coordinating Center (LDACC) [HHSN268201000029C]
- Broad Institute, Inc. through an SAIC-F subcontract to Van Andel Institute [10ST1035]
- University of Geneva [MH090941, MH101814]
- University of Chicago [MH090951, MH090937, MH101820, MH101825]
- University of North Carolina - Chapel Hill [MH090936, MH101819]
- Harvard University [MH090948]
- Stanford University [MH101782]
- Washington University St Louis [MH101810]
- University of Pennsylvania [MH101822]
- [DA006227]
- [DA033684]
- [N01MH000028]
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.
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