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

International Journal of Molecular Sciences

See-Hyoung Park¹  Minkyung Song²  Eunbi Yu³  Seyoung Yang³  Kitae Kwon³  Jung Yoen Park³  Jongsung Lee³  Seoyoun Yang³  Sae Woong Oh³  Seoyoung Choi³  Se Jung Park³  Su Bin Han³  Hyeyoun Kim³  Jae Youl Cho⁴ 

[1] Department of Bio and Chemical Engineering, Hongik University, Sejong City 30016, Korea;Integrative Research of T Cells Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, Korea;Molecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, Korea;Molecular Immunology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, Korea;

关键词: olfactory receptor (OR);    all-trans retinoic acid (ATRA);    cell proliferation;    calcium influx;    G-protein-coupled receptor (GPCR);    overexpression;   

DOI  :  10.3390/ijms222212304

来源: DOAJ

【 摘 要 】

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-trans 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 Ca²⁺ 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.

【 授权许可】

Unknown