Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo (original) (raw)
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Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging
Journal of Cosmetic Dermatology, 2005
Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by longterm exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.
2015
Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is central on aging of skin especially by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photodamage is exceedingly valued. Retinoids and alpha hydroxy acids have been endorsed by some researchers as possible candidates for protecting and or repairing the effect of UV damaged skin. For consolidating a better system of antiand protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblast’s elastin levels exposed...
Cellular retinoic acid binding protein-II expression and its potential role in skin aging
Aging, 2019
Skin aging is an intricate biological process consisting of intrinsic and extrinsic alterations of epidermal and dermal structures. Retinoids play an important role in epidermal cell growth and differentiation and are beneficial to counteract skin aging. Cellular retinoic acid binding protein-II (CRABP-II) selectively binds all transretinoic acid, the most active retinoid metabolite, contributing to regulate intracytoplasmic retinoid trafficking and keratinocyte differentiation. Immunohistochemistry revealed a reduced epidermal and dermal CRABP-II expression in aged human and mouse skin. To better clarify the role of CRABP-II, we investigated age-related skin changes in CRABP-II knockout mice. We documented an early reduction of keratinocyte layers, proliferation and differentiation rate, dermal and hypodermal thickness, pilosebaceous units and dermal vascularity in CRABP-II knockout compared with wild-type mice. Ultrastructural investigation documented reduced number and secretion of epidermal lamellar bodies in CRABP-II knockout compared with wild-type mice. Cultured CRABP-II knockout derived dermal fibroblasts proliferated less and showed reduced levels of TGF-β signal-related genes, Col1A1, Col1A2, and increased MMP2 transcripts compared with those from wildtype. Our data strongly support the hypothesis that a reduction of CRABP-II expression accelerates and promotes skin aging, and suggest CRABP-II as a novel target to improve the efficacy of retinoid-mediated antiaging therapies.
Advances in Dermatology and Allergology, 2019
Vitamin A is the first vitamin approved by the Food and Drug Administration as an anti-wrinkle agent that changes appearance of the skin surface and has anti-aging effects. Vitamin A is in a group of fat-soluble substances and belongs to the category of retinoids. Apart from retinol, that group includes structurally related substances with the biological properties of retinol. Since the biological activity of the substances differs, for the purpose of standardization, it is given in retinol equivalents. Vitamin A and its derivatives are among the most effective substances slowing the aging process. Retinoids regulate the cell apoptosis, differentiation and proliferation. Anti-wrinkle properties of retinoids promote keratinocytes proliferation, strengthen the protective function of the epidermis, restrain transepidermal water loss, protect collagen against degradation and inhibit metalloproteinases activity. Retinoid activity is related to high affinity for nuclear receptors: RAR-retinoid acid receptors and RXR-retinoid X receptors.
Retinoic acid receptor α expression and cutaneous ageing
Mechanisms of Ageing and Development, 2004
Intrinsic ageing of human skin is a subtle and gradual process that demonstrates few clinical or histological features until old age (>70 years). Initial work indicates that aged skin is “retinoid sensitive” but there is little data on the role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin ageing. As nuclear retinoid receptors have been implicated in ageing in rodents, we studied the distribution of these receptors in intrinsically aged as compared to young, photoprotected human skin. We found that intrinsic ageing of skin in vivo is accompanied by significant increases of RARα mRNA and protein whereas other isoforms show no alteration with age. In vitro transfection of COS-1 cells with the RARα gene induces expression of matrix metalloproteinase-1 (MMP-1), an enzyme known to play an active role in remodelling of the dermis in intrinsically aged and photoaged skin. Furthermore, addition of all-trans retinoic acid (RA) to cultures of RARα-transfected COS-1 cells diminishes RARα and returns levels of MMP-1 to those approaching baseline. These results demonstrate that intrinsic ageing of human skin is accompanied by significant elevation in the content of RARα and that over-expression of RARα influences expression of MMP-1, an important mediator of skin ageing.
Hyaluronic Acid in Dermal Rejuvenation: An in Vitro Study
Journal of biological regulators and homeostatic agents, 2015
The purpose of this paper is to evaluate the role of hyaluronic acid in bio-revitalization by testing several extracellular matrix biological parameters in cultured dermal fibroblasts. To this aim, fibroblastic expressed genes after exposition to three hyaluronic acid medical devices were evaluated. Cells were seeded on a layer of three different medical devices containing 6.2, 10 and 20 mg/ml of hyaluronic acid for 24 h. Real Time Polymerase Chain Reaction was performed to investigate gene expressions. Genes encoding hyaluronic acid synthesis and degradation, Metalloproteinases 2 and 3 and Desmoplakin production as well as GDF6, and IGF1 were activated by hyaluronic acid products. The in vitro study showed similar effects on tested genes despite a different concentration of hyaluronic acid contained in the medical devices and the simultaneous presence of other additives. Based on the reported data, gene activations are an aspect of metabolic modulation of signalling pathways rather...
Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores
International Journal of Cosmetic Science, 2019
INTRODUCTION: We report on the preparation and efficacy of 10-hydroxystearic acid (HSA) that improves facial age spots and conspicuous pores. METHODS: The hydration of oleic acid into HSA was catalyzed by the oleate hydratase from Escherichia coli. Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1 J cm À2) by immunohistochemistry on human ex vivo skin. UVB-induced expression of matrix metalloprotease-1 (MMP-1) was determined from full thickness skin by RT-qPCR. Modification of the fibroblast secretome by HSA was studied by mass-spectrometry-based proteomics. In a full-face, double blind, vehicle-controlled trial HSA was assessed for its effects on conspicuous facial pore size and degree of pigmentation of age spots in Caucasian women over an 8-week period. RESULTS: HSA was obtained in enantiomeric pure, high yield (≥80%). Collagen type I and type III levels were dose-dependently increased (96% and 244%; P < 0.01) in vitro and collagen type III in ex vivo skin by +57% (P < 0.01) by HSA. HSA also inhibited UVB-induced MMP-1 gene expression (83%; P < 0.01) and mitigated SBC induction (À34% vs. vehicle control) and reduced significantly UV-induced p53 up-regulation (À46% vs. vehicle control; P < 0.01) in irradiated skin. HSA modified the fibroblast secretome with significant increases in proteins associated with the WNT pathway that could reduce melanogenesis and proteins that could modify dermal fibroblast activity and keratinocyte differentiation to account for the alleviation of conspicuous pores. Docking studies in silico and EC50 determination in reporter gene assays (EC50 5.5 9 10 À6 M) identified HSA as a peroxisomal proliferator activated receptor-a (PPARa) agonist. Clinically, HSA showed a statistically significant decrease of surface and volume of skin pores (P < 0.05) after 8 weeks of application and age spots became significantly less pigmented than the surrounding skin (contrast, P < 0.05) after 4 weeks. CONCLUSION: HSA acts as a PPARa agonist to reduce the signs of age spots and conspicuous pores by significantly modulating the expression of p53, SBC, MMP-1 and collagen together with major changes in secreted proteins that modify keratinocyte, melanocyte and fibroblast cell behavior.