光老化
洛里克林
角质形成细胞
氧化应激
表皮(动物学)
细胞生物学
早衰
人体皮肤
DNA损伤
丝状蛋白
化学
生物
生物化学
总苞素
免疫学
体外
解剖
DNA
遗传学
特应性皮炎
作者
C. Y. Tan,Chew-Lim Tan,Toby Chin,Małgorzata Morenc,Chin Yee Ho,H. Rovito,Ling Shih Quek,Ai Ling Soon,John Lim,Oliver Dreesen,John E. Oblong,Sophie Bellanger
标识
DOI:10.1016/j.jid.2021.10.021
摘要
Nicotinamide (NAM), a NAM adenine dinucleotide precursor, is known for its benefits to skin health. Under standard culture conditions, NAM delays the differentiation and enhances the proliferation of human primary keratinocytes, leading to the maintenance of stem cells. In this study, we investigated the effects of NAM on photoaging in two-dimensional human primary keratinocyte cultures and three-dimensional organotypic epidermal models. In both models, we found that UVB irradiation and hydrogen peroxide induced human primary keratinocyte premature terminal differentiation and senescence. In three-dimensional organotypics, the phenotype was characterized by a thickening of the granular layer expressing filaggrin and loricrin, but thinning of the epidermis overall. NAM limited premature differentiation and ameliorated senescence, as evidenced by the maintenance of lamin B1 levels in both models, with decreased lipofuscin staining and reduced IL-6/IL-8 secretion in three-dimensional models, compared to those in UVB-only controls. In addition, DNA damage observed after irradiation was accompanied by a decline in energy metabolism, whereas both effects were partially prevented by NAM. Our data thus highlight the protective effects of NAM against photoaging and oxidative stress in the human epidermis and pinpoint DNA repair and energy metabolism as crucial underlying mechanisms.
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