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

Abstract

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.

MELTF Might Regulate Ferroptosis, Pyroptosis, and Autophagy in Platelet-Rich Plasma-Mediated Endometrial Epithelium Regeneration

“…The two main bioactive metabolites of vitamin A are all-trans-retinoic acid (atRA) and 11-cisretinaldehyde [22]. The atRA could promote cellular proliferation, differentiation, morphogenesis, cell survival, angiogenesis, wound recovery and stem cell migration mediated by the retinoic acid receptors (RARs) [23,24]. The atRA could inhibit the brosis of lung, liver and rein [25][26][27].…”

Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications

“…In the action of ATRA, RARα and RARγ inhibit proliferation of HaCaT KCs by down-regulating OR7A17, an olfactory receptor expressed in the skin. 82 After conducting further investigation into RAR subtypes, it was discovered that the signalling pathways mediated by RARα and RARγ exhibit distinct effects within the epidermis.…”

“…Despite the widespread use of retinoic acid drugs in treating acne, the specific function of RAR isoforms at the molecular or cellular level are not fully elucidated. In the action of ATRA, RAR‐α and RAR‐γ inhibit proliferation of HaCaT KCs by down‐regulating OR7A17, an olfactory receptor expressed in the skin 82 . After conducting further investigation into RAR subtypes, it was discovered that the signalling pathways mediated by RAR‐α and RAR‐γ exhibit distinct effects within the epidermis.…”

Proteinase K/Retinoic Acid-Loaded Cationic Liposomes as Multifunctional Anti-Acne Therapy to Disorganize Biofilm and Regulate Keratinocyte Proliferation

“…C. acnes impairs epidermal barrier property by stimulating keratinocyte proliferation. 51 It was inferred that topical liposomes could facilely penetrate the skin to inhibit C. acnes infection, arresting inflammation and keratinocyte hyperproliferation to effectively treat the infected wound.…”