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Effects of B[a]P-UVA Co-Exposure on Epigenetic m.rks of Isolated Skin Cells and Im.act of an Arundo donax L. Extract of These Changes

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Journal of Cosm.tics, Derm.tological Sciences and Applications 2024年第3期14卷 253-269页

作者： marie m. dorr m.gali Favre-m.rcuret Katell Vié Richard Fitoussi Laboratoires Clarins Pontoise France

Background: Extrinsic aging results from.environm.ntal stressors such as UVR or pollutants. While the effects of single pollutants are better understood, those of their com.ination rem.in poorly scrutinized. Objective: Building on a study showing downregulation of several processes upon co-exposure to B[a]P and UVA, we investigated changes induced by epigenetic m.rks. m.terials and m.thods: Hum.n prim.ry fibroblasts and HaCaT cells were exposed to B[a]P and UVA. After 24 hours, exposed and unexposed cells were com.ared to assess DNA m.thylation. Focusing on HaCaT, m.ltiplex assays enabled quantifying histone H3 m.difications and evaluating four splicing factors (SRSF1, SRSF3, SFPQ, and SF3B1) by im.unohistochem.cal labeling. The expression of keratinocyte-/fibroblast-relevant genes was assessed by RT-qPCR. Finally, the im.act of an Arundo donax L. extract added 24 hours before B[a]P-UVA co-exposure was analyzed. Results: Exposure to B[a]P-UVA raised DNA m.thylation (HaCaT: ×3.6, fibroblasts: ×1.9), an increase prevented by the extract. In HaCaT cells, B[a]P-UVA increases the frequency of S10P (+38%). When exposure was preceded by extract treatm.nt, the frequency of several m.thylations was im.acted. B[a]P-UVA only induced the expression of SRSF1 and SFPQ in HaCaT (+46% and +34%). Treatm.nt with the extract abolished this effect. Co-exposure increases the expression of inflam.ation-related genes (IL-1α, IL-1β) in HaCaT cells and decreases those of AQP3, KRT15, and SOD2. The extract has little effect on these changes. In prim.ry fibroblasts, exposure to B[a]P-UVA lowered the expression of LOXL2, LUm. and TGFBR2 (−38%, −59%, and −51%, respectively), and the extract did not affect these m.difications. Conclusion: Within 24 hours, a single B[a]P-UVA co-exposure changes epigenetic m.rks of skin cells but has only m.ld effects on gene expression. An Arundo donax L. extract can prevent part of the epigenetic m.rks’ changes and could stim.late the expression of som. genes in

关键词： Extrinsic Aging DNA m.thylation Histone H3 Splicing Factors Arundo donax L.

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