Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells

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-<i>tra...

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Autores principales:	Hyeyoun Kim, See-Hyoung Park, Sae Woong Oh, Kitae Kwon, Se Jung Park, Eunbi Yu, Seyoung Yang, Jung Yoen Park, Seoyoung Choi, Seoyoun Yang, Su Bin Han, Minkyung Song, Jae Youl Cho, Jongsung Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	olfactory receptor (OR) all-trans retinoic acid (ATRA) cell proliferation calcium influx G-protein-coupled receptor (GPCR) overexpression Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/ba993de0c39040a5b5339bfe37a69d13
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spelling	oai:doaj.org-article:ba993de0c39040a5b5339bfe37a69d132021-11-25T17:55:13ZOlfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells10.3390/ijms2222123041422-00671661-6596https://doaj.org/article/ba993de0c39040a5b5339bfe37a69d132021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12304https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Olfactory 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-<i>trans</i> 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<sup>2+</sup> 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.Hyeyoun KimSee-Hyoung ParkSae Woong OhKitae KwonSe Jung ParkEunbi YuSeyoung YangJung Yoen ParkSeoyoung ChoiSeoyoun YangSu Bin HanMinkyung SongJae Youl ChoJongsung LeeMDPI AGarticleolfactory receptor (OR)all-trans retinoic acid (ATRA)cell proliferationcalcium influxG-protein-coupled receptor (GPCR)overexpressionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12304, p 12304 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	olfactory receptor (OR) all-trans retinoic acid (ATRA) cell proliferation calcium influx G-protein-coupled receptor (GPCR) overexpression Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	olfactory receptor (OR) all-trans retinoic acid (ATRA) cell proliferation calcium influx G-protein-coupled receptor (GPCR) overexpression Biology (General) QH301-705.5 Chemistry QD1-999 Hyeyoun Kim See-Hyoung Park Sae Woong Oh Kitae Kwon Se Jung Park Eunbi Yu Seyoung Yang Jung Yoen Park Seoyoung Choi Seoyoun Yang Su Bin Han Minkyung Song Jae Youl Cho Jongsung Lee Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells
description	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-<i>trans</i> 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<sup>2+</sup> 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.
format	article
author	Hyeyoun Kim See-Hyoung Park Sae Woong Oh Kitae Kwon Se Jung Park Eunbi Yu Seyoung Yang Jung Yoen Park Seoyoung Choi Seoyoun Yang Su Bin Han Minkyung Song Jae Youl Cho Jongsung Lee
author_facet	Hyeyoun Kim See-Hyoung Park Sae Woong Oh Kitae Kwon Se Jung Park Eunbi Yu Seyoung Yang Jung Yoen Park Seoyoung Choi Seoyoun Yang Su Bin Han Minkyung Song Jae Youl Cho Jongsung Lee
author_sort	Hyeyoun Kim
title	Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells
title_short	Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells
title_full	Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells
title_fullStr	Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells
title_full_unstemmed	Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells
title_sort	olfactory receptor or7a17 expression correlates with all-<i>trans</i> retinoic acid (atra)-induced suppression of proliferation in human keratinocyte cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ba993de0c39040a5b5339bfe37a69d13
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Olfactory Receptor OR7A17 Expression Correlates with All-<i>Trans</i> Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells

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