Epigenetic regulation is increasingly considered to play an important role in photoaging. UV irradiation induces global histone acetylation not only by decreasing histone deacetylases and stimulating histone acetyltransferases but also by locally reducing the level of histone acetylation. This epigenetic regulation may induce diverse modifications in the extracellular matrix structure. In this study, we observed the impact of specific acetylation on global histone modifications and their impact on the expression of dermal proteins involved in skin elasticity. We used shotgun-MS analysis to identify a common global profile of histone post-translational modifications induced in fibroblasts by UVA and HDAC inhibitors (NaBu: sodium butyrate and/or (TSA:Trichostatin). AlphaLISA or immunostaining were used to evaluate H3K27 acetylation. Western Blot analysis were done for fibulin 5 and MMP1. The efficacy of a plant extract was finally evaluated. 57 peptides were regulated in the UVA-exposed condition (38 upregulated and 19 downregulated) compared with the non-treated condition, but only 26 peptides were regulated after TSA (20 upregulated and 6 downregulated), indicating a greater impact of UVA than TSA on epigenetic regulation linked to histones. We also observed more acetylation than methylation taking place when fibroblasts were exposed to 10 J/cm2 UVA. Immunostaining evidenced a stronger impact of 20 mM NaBu than 7.5 J/cm2 UVA on H3K27 acetylation increase that was confirmed by AlphaLISA (NaBu x7.4). In parallel, fibulin 5 was decreased after UVA irradiation and NaBu treatment (-68% and -85% respectively), whereas MMP1 was increased (+28% and +20%). Finally, we showed that a litchi pericarp extract reduced the H3K27acetylation level induced by NaBu or UVA (by 2.2 and 2 folds respectively) and fully compensated the UVA-induced fibulin decrease and MMP1 increase (+132% and -84% vs UVA respectively). This is the first-time description of the contribution of histone H3K27 acetylation to UVA-induced epigenetic regulation of the fibulin 5 and MMP1 and a first step in the selection of active ingredients.

ESDR231 - H3K27 acetylation modulation to prevent UVA-induced photoaging

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.