Vitamin A and its derivatives, particularly retinol, slow both chronological and photo-induced aging processes. Retinol reduces the appearance of wrinkles and the decrease of the skin firmness and elasticity by protecting against collagen and elastin fiber changes. In addition to retinol’s rejuvenating skin benefits through direct transcriptional activation, recent studies also suggest an epigenetic regulation through micro-RNAs (miRNAs) modulation. We investigated how retinol supports the stimulation of type I collagen and elastin through proteomic, transcriptomic and epigenetic miRNA-expression changes in human skin fibroblasts. Five miRNAs, previously described as targeting collagen or elastin gene expression, were particularly studied after validation of their expression in normal human fibroblasts by miRNA sequencing analysis. Retinol treatment was applied on monolayered cultures of dermal fibroblasts and the levels of the 5 selected miRNAs (miR-181b, Let-7b-5p, miR-29b-3p, miR-195-5p and miR-497-5p) were quantified by q-RT-PCR. We observed that retinol was able to reduce the expression of the 5 studied collagen- or elastin-inhibiting miRNAs. After retinol treatment, miR-181b (related to elastin protein) and Let7b (related to collagen protein) were respectively decreased by 39% and 37% In addition, miR-29b, miR-195 and miR-497, which regulate both collagen and elastin proteins, were respectively decreased by 24%, 49% and 42% after retinol treatment. In addition, retinol simultaneously stimulated both Elastin and collagen type I proteins by 38% and 296% respectively. These experiments efficiently characterize the epigenetic activity of retinol through inhibition of specific miRNAs. This may contribute to increase the knowledge on retinol mode of action related to rejuvenating skin benefits.

ESDR167 - Contribution of miRNAs as epigenetic regulators of Retinol efficacy in the skin dermis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING