421 Involvement of olfactory receptor OR2AT4 in skin aging and the response to environmental pollution

Abstract

Olfactory receptors (ORs) are 7-transmembrane G protein-coupled receptors expressed in the olfactory epithelium and mediate the odor perception. Around 400 ORs are known in human, and their expression has been evidenced in various peripheral tissues such as intestinal epithelium, prostate, spermatozoa, liver, and skin. These ectopic receptors might regulate physiological functions beyond olfaction. The OR called OR2AT4 is expressed in the skin, especially the epidermal keratinocytes, melanocytes, dendritic cells, and hair follicles. Its activation increases the proliferation and migration of keratinocytes, allowing faster re-epithelialization during wound healing. OR2AT4 downregulation induces the decrease of IGF-1 expression in hair follicles suggesting its link with hair growth. However, the roles of ORs in the skin are still incompletely described, especially, the possible link with intrinsic and extrinsic aging. In this study, OR2AT4 expression was investigated in various senescent skin models in vitro, such as human cultured keratinocytes, and reconstructed epidermises. Besides, the consequences of ultrafine particle-induced skin damage were studied via the evaluation of OR2AT4 expression level and on markers involved in skin senescence and differentiation. In parallel, botanical extracts were screened for their ability to modulate the expression of OR2AT4 and related markers. Our results showed that the expression of OR2AT4 was inversely correlated with aging and UFP-induced skin damage, suggesting that its modulation could be beneficial to limit the consequences of intrinsic and extrinsic aging into the skin.