Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.
Int J Mol Sci. 2021 Mar 10;22(6):2799. doi: 10.3390/ijms22062799.
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, , , 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.
嗅觉受体（ORs）在各种细胞类型中具有多样化的生理作用，超出了其在嗅上皮中作为气味传感器的功能。这些先前的发现表明，ORs 可以作为几种病理状况的诊断标志物和有前途的治疗靶点。在本研究中，我们试图表征暴露于紫外线（UV）光或炎症下的 HaCaT 人角质形成细胞系中 ORs 表达的变化，这些是公认的破坏皮肤屏障的刺激因素。我们证实，主要嗅觉信号成分，包括 ORs、、、和腺苷酸环化酶 3，在 HaCaT 细胞中高度表达。我们还表明，在 HaCaT 细胞中可检测到的 12 个异位 ORs 在 UV 照射或炎症条件下的表达高于正常条件。我们进一步评估了在已知 OR 气味配体存在下 HaCaT 细胞中特定 OR 介导的生物学反应，并观察到特定配体激活的 ORs 下调 HaCaT 细胞中的皮肤屏障基因。本研究表明 OR 作为皮肤屏障异常的标志物的潜力。需要进一步研究来探索 OR 如何参与屏障功能障碍的发展和进展。
