Abstract
Skin is a direct target of fine particulate matter (PM2.5), as it is constantly exposed. Herein, we investigate whether Korean red ginseng (KRG) can inhibit PM2.5-induced senescence in skin keratinocytes. PM2.5-treated human keratinocyte cell lines and normal human epidermal keratinocytes showed characteristics of cellular senescence, including flat and enlarged forms; however, KRG suppressed them in both cell types. Moreover, while cells exposed to PM2.5 showed a higher level of p16INK4A expression (a senescence inducer), KRG inhibited its expression. Epigenetically, KRG decreased the expression of the ten-eleven translocation (TET) enzyme, a DNA demethylase induced by PM2.5, and increased the expression of DNA methyltransferases suppressed by PM2.5, resulting in the decreased methylation of the p16INK4A promoter region. Additionally, KRG decreased the expression of mixed-lineage leukemia 1 (MLL1), a histone methyltransferase, and histone acetyltransferase 1 (HAT1) induced by PM2.5. Contrastingly, KRG increased the expression of the enhancer of zeste homolog 2, a histone methyltransferase, and histone deacetyltransferase 1 reduced by PM2.5. Furthermore, KRG decreased TET1, MLL1, and HAT1 binding to the p16INK4A promoter, corresponding with the decreased mRNA expression of p16INK4A. These results suggest that KRG exerts protection against the PM2.5-induced senescence of skin keratinocytes via the epigenetic regulation of p16INK4A.