UV-Irradiation- and Inflammation-Induced Skin Barrier Dysfunction Is Associated with the Expression of Olfactory Receptor Genes in Human Keratinocytes

Abstract

Olfactory receptors (ORs) have diverse physiological roles in various cell types, beyond their function as odorant sensors in the olfactory epithelium. These previous findings have suggested that ORs could be diagnostic markers and promising therapeutic targets in several pathological conditions. In the current study, we sought to characterize the changes in the expression of ORs in the HaCaT human keratinocytes cell line exposed to ultraviolet (UV) light or inflammation, well-recognized stimulus for skin barrier disruption. We confirmed that major olfactory signaling components, including ORs, GNAL, Ric8b, and adenylate cyclase type 3, are highly expressed in HaCaT cells. We have also demonstrated that the 12 ectopic ORs detectable in HaCaT cells are more highly expressed in UV-irradiated or inflamed conditions than in normal conditions. We further assessed the specific OR-mediated biological responses of HaCaT cells in the presence of known odorant ligands of ORs and observed that specific ligand-activated ORs downregulate skin barrier genes in HaCaT cells. This study shows the potential of OR as a marker for skin barrier abnormalities. Further research is needed to explore how OR is implicated in the development and progression of barrier dysfunction.

Dermal Olfactory Receptor OR51B5 Is Essential for Survival and Collagen Synthesis in Human Dermal Fibroblast (Hs68 Cells)

“…Although the produced cAMP is mainly associated with the transmission of odor signals to the olfactory system in the brain, a transient increase in intracellular cAMP also stimulates the downstream PKA-CREB pathway, which modulates various pathological and physiological functions [33][34][35][36]. Notably, olfactory signaling components are distributed not only in the olfactory cells; however, several studies, including our previous work, have demonstrated that several cell types in ectopic tissues constitutively express olfactory transduction machinery components, such as ORs, GNAL, ric8b, and ADCY3 [19,32,37,38]. Consistent with the results of previous studies, we confirmed that major olfactory signaling components, such as ORs, GNAL, ric8b, and ADCY3, are expressed in human dermal fibroblasts.…”

α-Ionone protects against UVB-induced photoaging in epidermal keratinocytes

“…As UVB could damage the barrier function ( Kang et al, 2021 ), we detected the mRNA expression variation of barrier-related proteins in UVB-irradiated and non-UVB-irradiated HaCaT cells. Our results showed that UVB irradiation significantly decreases barrier-related genes, containg keratin 1 , filaggrin , and keratin 10 ( Fig.…”

“…Thereafter, other barrier-related proteins are attached to this scaffold, completing the corneocyte backbone with lipids ( Jensen and Proksch, 2009 , Van Smeden et al, 2014 ). UV irradiation is the major cause for disruption of the epidermal barrier function, accompanied by decrease in keratin and filaggrin levels, even causing skin inflammation ( Kang, Son, Park, Choi, & Park, 2021 ).…”

Odorant Binding Causes Cytoskeletal Rearrangement, Leading to Detectable Changes in Endothelial and Epithelial Barrier Function and Micromotion

“…Interestingly, ORs are expressed in a variety of non-olfactory cells and influence many physiological processes (reviewed in [ 8 ]). In non-olfactory cells, intracellular signaling initiated by OR binding can result in increased survival, proliferation, and migration, among other cellular effects, via cAMP or other second messengers, which stimulate diverse signaling pathways [ 9 , 10 , 11 ]. Even though distinct, physiologically relevant pathways are activated in non-olfactory cells after odorant binding, the olfactory receptor is a GPCR, which initiates signaling via G-proteins.…”