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DIFFERENTIAL MODULATION OF ECM COMPONENTS AND GFR BY RETINOIC ACID AND A PHYSIOLOGICALLY BALANCED GF FORMULATION.

Vega1, V.L., Mehta1, R.C., Bachelor2, M.A., Oldach2, J., Bolmarcich2, J. and Armento2, A.J.  1Research & Development, SkinMedica, Inc. An Allergan Company. 2MatTek Corporation.
Abstract

Overall appearance of skin is a combination of health, ethnicity, lifestyle and age, which determine skin color, texture, firmness and smoothness. Uneven color, rough, lax and wrinkled skin are associated with aged skin. Microscopically, aged skin has an atrophic epidermis, flattened dermal-epidermal junction, decreased number of dermal fibroblasts and diminished synthesis of extracellular matrix components and growth factors (GF). Treatment with topical formulations that contain a physiologically balanced and stable GF mixture has shown to improve skin appearance. Environmental conditions such as solar UV-light strongly modulate skin appearance triggering premature aging or “photoaging”. Retinoids are the gold standard for the treatment of photoaged skin. Retinoic acid (RA) is recognized by the FDA for the treatment of photo-aging. The goal of this study was to compare the effect of a physiologically balance GF formulation (PB-GFF) and generic RA (0.05%) on simulated solar (SS)-UV-light treated skin. In brief, EpiDermFT™ tissues were produced in the MatTek Corporation and subjected or not to SS-UV-light radiation (200 mJ/cm2, 20 min). Immediately after UV-exposure, tissues were treated with 25 µl of PB-GFF or RA and allowed to recover for 12 and 24 h. Total mRNA was isolated and expression of different genes were analyzed by PCR. The results show that all treated groups have a significant increase in COL1A1 and COL3A1 expression in comparison with untreated tissues, although the kinetics and intensity of these increases were different. ELN and elastin-related proteins (LOXL1 and MFAP2) mRNA levels were also significantly induced (24 h after UV-exposure). Changes in the mRNA expression of GF-receptors (FGFR and EGFR) were also observed. Non-physiologically balanced GF formulations did not trigger any changes in the genes previously mentioned. These data demonstrate that both RA and PB-GFF induce synthesis of key ECM components in EpiDermFT tissues, and therefore may be beneficial for preventing skin damage and reverting photo-aging.

Keywords

COL1A1, COL3A1, EGF receptor, Elastin related proteins, EFT-400, Extracellular matrix components, FGF receptor, Hyaluronic acid, LOXL1, MFAP2, MMP-1, Photoaging, Skin aging, Skin wrinkling, SOD1, TIMP-1

Materials Tested

Growth factors, Retinoic acid, UV light

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