Retinoic acid ameliorates photoaged skin through RAR‑mediated pathway in mice.

Retinoic acid (RA), the bioactive metabolite of vitamin A, has demonstrated efficacy in the treatment of photo-aged skin; however, the mechanism of action of RA remains unclear. The aim of the present study was to examine whether the therapeutic effects of RA on photoaged skin are mediated by retinoic acid receptor (RAR) and/or retinoid X receptor (RXR) in mice, and to investigate the underlying mechanism. Photoaged skin in Imprinting Control Region mice was induced by repeated exposure to ultraviolet (UV) irradiation. Mice were randomly divided into nine groups: Normal; UV control; all-trans retinoic acid (ATRA); ATRA + RAR antagonist; ATRA + RXR antagonist; RAR agonist; RAR agonist + RAR antagonist; RXR agonist; and RXR agonist + RXR antagonist. Masson's trichrome staining was used to examine skin collagen fibers. Hydroxyproline assays were used to determine collagen content. The protein expression of matrix metalloproteinase (MMP)-3, MMP-13, type I procollagen, c-Jun and c-Fos was detected using western blot analysis. The results demonstrated that ATRA and RAR agonist ameliorated the UV-induced damage to skin collagen fibers, and increased the collagen content in photoaged skin through RAR. Furthermore, ATRA and RAR agonist stimulated type I procollagen protein expression, and inhibited MMP-3, MMP-13 and c-Jun protein expression through RAR in photoaged skin. However, ATRA and RAR agonist exhibited no significant effect on the protein expression of c-Fos in photoaged skin. These findings suggest that RA ameliorates photoaged skin through a RAR-mediated signaling pathway in mice.