Reactivating the extracellular matrix synthesis of sulfated glycosaminoglycans and proteoglycans to improve the human skin aspect and its mechanical properties

Abstract

BackgroundThe aim of this study was to demonstrate that a defined cosmetic composition is able to induce an increase in the production of sulfated glycosaminoglycans (sGAGs) and/or proteoglycans and finally to demonstrate that the composition, through its combined action of enzyme production and synthesis of macromolecules, modulates organization and skin surface aspect with a benefit in antiaging applications.Materials and methodsGene expression was studied by quantitative reverse transcription polymerase chain reaction using normal human dermal fibroblasts isolated from a 45-year-old donor skin dermis. De novo synthesis of sGAGs and proteoglycans was determined using Blyscan™ assay and/or immunohistochemical techniques. These studies were performed on normal human dermal fibroblasts (41- and 62-year-old donors) and on human skin explants. Dermis organization was studied either ex vivo on skin explants using bi-photon microscopy and transmission electron microscopy or directly in vivo on human volunteers by ultrasound technique. Skin surface modification was investigated in vivo using silicone replicas coupled with macrophotography, and the mechanical properties of the skin were studied using Cutometer.ResultsIt was first shown that mRNA expression of several genes involved in the synthesis pathway of sGAG was stimulated. An increase in the de novo synthesis of sGAGs was shown at the cellular level despite the age of cells, and this phenomenon was clearly related to the previously observed stimulation of mRNA expression of genes. An increase in the expression of the corresponding core protein of decorin, perlecan, and versican and a stimulation of their respective sGAGs, such as chondroitin sulfate and heparan sulfate, were found on skin explants. The biosynthesis of macromolecules seems to be correlated at the microscopic level to a better organization and quality of the dermis, with collagen fibrils having homogenous diameters. The dermis seems to be compacted as observed on images obtained by two-photon microscopy and ultrasound imaging. At the macroscopic level, this dermis organization shows a smoothed profile similar to a younger skin, with improved mechanical properties such as firmess.ConclusionThe obtained results demonstrate that the defined cosmetic composition induces the synthesis of sGAGs and proteoglycans, which contributes to the overall dermal reorganization. This activity in the dermis in turn impacts the surface and mechanical properties of the skin.

Extracellular proteoglycan decorin maintains human hair follicle stem cells

“…If DCN acts as a niche component to maintain HFSC and the decrease in the number of HFSC is caused by age‐related changes in the niche, DCN expression may reduce with age. We performed immunohistochemistry against DCN and found that DCN was strongly expressed across the dermis, as shown in the previous study . We observed DCN signals at a higher magnification so that the strong DCN signal in the dermis did not impede close observation and quantification of DCN localization in the area around HFSC.…”

“…We performed immunohistochemistry against DCN and found that DCN was strongly expressed across the dermis, as shown in the previous study. 25 We observed DCN signals at a higher magnification so that the strong DCN signal in the dermis did not impede close observation and quantification of DCN localization in the area around HFSC. It was shown that DCN was localized on the basement membrane alongside KRT15-positive HFSC in young subjects and the DCN signal as well as the KRT15 signal were remarkably reduced with age ( Fig.…”

Glycosaminoglycans: Sweet as Sugar Targets for Topical Skin Anti-Aging

“… 121 Chajra and co-workers utilized a similar strategy for boosting sulfated GAG levels with a formulation containing GAG precursors and synthesis intermediaries, finding it increased sulfated GAG levels within cultured human skin fibroblasts and ex vivo human skin, while improving dermal structure of ex vivo skin samples and increasing skin smoothness in a cohort of female volunteers. 122 Jasmonic acid derivatives (JAD) have also been demonstrated to increase proteoglycan expression and modify GAG fine structure in skin, as well as potentiate KGF signaling. Consistent with these in vitro data, JAD treatment promotes re-epithelialization clinically within a suction-cup blister model of wound healing.…”

Anti‑apoptotic effects of glycosaminoglycans via inhibition of ERK/AP‑1 signaling in TNF‑α‑stimulated human dermal fibroblasts

“…The various anti-aging benefits of GAGs have contributed to their widespread inclusion in cosmetic and pharmaceutical products (50,51). GAGs, including hyaluronic acid, chondroitin sulfate, dermatan sulfate and keratan sulfate are abundant structural components of extracellular structures and regulate many biological processes, including cell growth, migration, differentiation, adhesion and lipid synthesis in the dermis and epidermis (1,(52)(53)(54)(55)(56). The contents of GAGs change during intrinsic and extrinsic aging (57)(58)(59)(60).…”

“…The modulation of collagen synthesis/degradation is thus a pivotal target for anti-wrinkle agents. Glycosaminoglycans (GAGs) are highly charged polysaccharides that are an important structural component of the extracellular matrix (ECM) and are often used in cosmetic products (1)(2)(3). In a previous clinical trial, it was identified that a cream containing GAGs regulated wrinkles, skin elasticity, dermal density and skin tightening (4).…”