Molecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, Korea.
Department of Bio and Chemical Engineering, Hongik University, Sejong City 30016, Korea.
Int J Mol Sci. 2021 Nov 14;22(22):12304. doi: 10.3390/ijms222212304.
Olfactory receptors (ORs), which belong to the G-protein-coupled receptor family, have been widely studied as ectopically expressed receptors in various human tissues, including the skin. However, the physiological functions of only a few OR types have been elucidated in skin cells. All- retinoic acid (ATRA) is a well-known medication for various skin diseases. However, many studies have shown that ATRA can have adverse effects, resulting from the suppression of cell proliferation. Here, we investigated the involvement of OR7A17 in the ATRA-induced suppression of human keratinocyte (HaCaT) proliferation. We demonstrated that OR7A17 is expressed in HaCaT keratinocytes, and its expression was downregulated by ATRA. The ATRA-induced downregulation of OR7A17 was attenuated via RAR α or RAR γ antagonist treatment, indicating that the effects of ATRA on OR7A17 expression were mediated through nuclear retinoic acid receptor signaling. Moreover, we found that the overexpression of OR7A17 induced the proliferation of HaCaT cells while counteracting the antiproliferative effect of ATRA. Mechanistically, OR7A17 overexpression reversed the ATRA-induced attenuation of Ca entry. Our findings indicated that ATRA suppresses cell proliferation through the downregulation of OR7A17 via RAR α- and γ-mediated retinoid signaling. Taken together, OR7A17 is a potential therapeutic target for ameliorating the anti-proliferative effects of ATRA.
嗅觉受体（ORs）属于 G 蛋白偶联受体家族，已被广泛研究为各种人体组织（包括皮肤）中异位表达的受体。然而，只有少数几种 OR 类型在皮肤细胞中的生理功能已被阐明。全反式维甲酸（ATRA）是一种用于治疗各种皮肤病的知名药物。然而，许多研究表明，ATRA 可能会产生不良反应，这是由于其对细胞增殖的抑制作用。在这里，我们研究了 OR7A17 在 ATRA 诱导的人角质形成细胞（HaCaT）增殖抑制中的作用。我们证明了 OR7A17 在 HaCaT 角质形成细胞中表达，并被 ATRA 下调。通过 RAR α 或 RAR γ 拮抗剂处理，ATRA 诱导的 OR7A17 下调得到减弱，表明 ATRA 对 OR7A17 表达的影响是通过核视黄酸受体信号转导介导的。此外，我们发现 OR7A17 的过表达诱导 HaCaT 细胞增殖，同时抵消了 ATRA 的抗增殖作用。从机制上讲，OR7A17 的过表达逆转了 ATRA 诱导的 Ca 内流衰减。我们的研究结果表明，ATRA 通过 RAR α 和 γ 介导的视黄酸信号下调 OR7A17 抑制细胞增殖。总之，OR7A17 是改善 ATRA 抗增殖作用的潜在治疗靶点。
