Dermal Olfactory Receptor OR51B5 Is Essential for Survival and Collagen Synthesis in Human Dermal Fibroblast (Hs68 Cells)

Abstract

Skin dermis comprises extracellular matrix components, mainly collagen fibers. A decrease in collagen synthesis caused by several factors, including ultraviolet (UV) irradiation and stress, eventually causes extrinsic skin aging. Olfactory receptors (ORs) were initially considered to be specifically expressed in nasal tissue, but several ORs have been reported to be present in other tissues, and their biological roles have recently received increasing attention. In this study, we aimed to characterize the role of ORs in cell survival and collagen synthesis in dermal fibroblasts. We confirmed that UVB irradiation and dexamethasone exposure significantly decreased cell survival and collagen synthesis in Hs68 dermal fibroblasts. Moreover, we demonstrated that the mRNA expression of 10 ORs detectable in Hs68 cells was significantly downregulated in aged conditions compared with that in normal conditions. Thereafter, by individual knockdown of the 10 candidate ORs, we identified that only OR51B5 knockdown leads to a reduction of cell survival and collagen synthesis. OR51B5 knockdown decreased cAMP levels and dampened the downstream protein kinase A/cAMP-response element binding protein pathway, downregulating the survival- and collagen synthesis-related genes in the dermal fibroblasts. Therefore, OR51B5 may be an interesting candidate that plays a role in cell survival and collagen synthesis.

Poly‐L‐Lactic acid increases collagen gene expression and synthesis in cultured dermal fibroblast (Hs68) through the TGF‐β/Smad pathway

“…As PLLA particles degrade, they gradually regain volume by stimulating collagen synthesis, and thus, PLLA is widely used as a dermal filler to improve appearance and repair imperfections, as well as in various areas of medicine 19,20 . The Hs68 cell line has the typical characteristics of primary dermal fibroblasts and is the most widely used dermal fibroblast cell line in the study of dermal physiology, which can regulate various components of the cell matrix including collagen 4,21 . Therefore, we explored the regulation of collagen synthesis in dermal cells by PLLA in Hs68 cells and focused on its potential molecular mechanisms.…”

“…19,20 The Hs68 cell line has the typical characteristics of primary dermal fibroblasts and is the most widely used dermal fibroblast cell line in the study of dermal physiology, which can regulate various components of the cell matrix including collagen. 4,21 Therefore, we explored the regulation of collagen synthesis in dermal cells by PLLA in Hs68 cells and focused on its potential molecular mechanisms.…”

“…Collagen, a major component of the extracellular matrix (ECM), is synthesized by dermal fibroblasts to maintain the skin's strength and elasticity 3 . However, UV rays, skin inflammation, intracellular metabolites, and aging can inhibit collagen synthesis, leading to skin aging occurrences such as wrinkle formation, sagging, and laxity 4 . While the current anti‐aging process cannot be permanently improved, injectable fillers are a simple, fast‐acting, less‐invasive, and fast‐recovery cosmetic procedure to combat skin aging 5 …”

“…3 However, UV rays, skin inflammation, intracellular metabolites, and aging can inhibit collagen synthesis, leading to skin aging occurrences such as wrinkle formation, sagging, and laxity. 4 While the current anti-aging process cannot be permanently improved, injectable fillers are a simple, fast-acting, less-invasive, and fast-recovery cosmetic procedure to combat skin aging. 5 As demand increases, safe and effective facial fillers are being updated, such as biodegradable calcium hydroxyapatite, polycaprolactone, hyaluronic acid, and non-biodegradable poly-meth methacrylate silicone, polyacrylamide, and autologous fat grafting.…”

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

“…In our study, we focused on type 1 collagen, a crucial protein that imparts strength and elasticity to the skin. It is well-documented that the production of this protein decreases not only due to intrinsic factors but also to extrinsic factors such as exposure to ultraviolet light and glucocorticoids, resulting in skin aging characterized by wrinkles and sagging skin [ 31 , 32 , 33 ]. We harnessed the potential of cAMP to counteract glucocorticoid activity, mitigating the decrease in collagen production in dermal fibroblasts caused by stress.…”