Activation of OR10A3 by Suberic Acid Promotes Collagen Synthesis in UVB-Irradiated Dermal Fibroblasts via the cAMP-Akt Pathway

Abstract

In recent years, there has been a great deal of interest in the ectopic roles of olfactory receptors (ORs) throughout the human body. Especially, the ectopic function of OR in the skin is one of the most actively researched areas. Suberic acid, a scent compound, was hypothesized to increase collagen synthesis in the ultraviolet B (UVB)-irradiated human dermal fibroblasts (Hs68) through a specific olfactory receptor. Suberic acid ameliorated UVB-induced decreases in collagen production in Hs68 cells. Using in silico docking to predict the binding conformation and affinity of suberic acid to 15 ectopic ORs detectable in Hs68, several ORs were identified as promising candidates. The effect of suberic acid on collagen synthesis in UVB-exposed dermal fibroblasts was nullified only by a reduction in OR10A3 expression via specific siRNA. In addition, using the cells transiently expressing OR10A3, we demonstrated that suberic acid can activate OR10A3 by assessing the downstream effector cAMP response element (CRE) luciferase activity. We examined that the activation of OR10A3 by suberic acid subsequently stimulates collagen synthesis via the downstream cAMP-Akt pathway. The findings support OR10A3 as a promising target for anti-aging treatments of the skin.

Integrated Secondary Metabolomic and Antioxidant Ability Analysis Reveals the Accumulation Patterns of Metabolites in Momordica charantia L. of Different Cultivars

“…JAs are involved in the regulation of important plant growth and development, and especially the mediation of plant responses to biotic and abiotic stresses, which can inhibit Rubisco biosynthesis, induce stomatal opening and affect the uptake of nitrogen and phosphorus and the transport of organic matter such as glucose [62]. Suberic acid is abundant in several plants, including Vernonia galamensis, castor, and Hibiscus syriacus [63]. We also identified an increase in suberic acid in bitter gourd (Table S2).…”

The Role of Cyclic Adenosine Monophosphate (cAMP) in Modulating Glucocorticoid Receptor Signaling and Its Implications on Glucocorticoid-Related Collagen Loss

“…Numerous studies, including our own previous work, have reported that cAMP itself has the ability to control collagen production through a variety of mechanisms independent of stress; however, consensus on the direction of regulation has not yet been reached. Some studies propose that an increase in cAMP levels could potentially promote the production of type 1 collagen [ 46 , 47 , 48 ], while others have shown that an increase in cAMP may, in fact, suppress this process [ 49 , 50 , 51 ]. The exact reason for this discrepancy remains largely unclear, but the extent of the increase in cAMP has been suggested as a potential determinant of collagen regulation.…”

Medium-chain dicarboxylic acids: chemistry, pharmacological properties, and applications in modern pharmaceutical and cosmetics industries

“…A therapeutic target for skin anti-ageing may be OR10A3. 101 However, studies on the topical use of SUBA in cosmetics have not been reported.…”