Pangilinan Neil Dominic T, Shalbaf Mohammad, Souza Aline, Chavan Bhaven, Bonn Catherine, Birch-Machin Mark A
Dermatological Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.
Croda Europe Ltd, Snaith, UK.
FASEB J. 2025 May 15;39(9):e70568. doi: 10.1096/fj.202500342R.
Inorganic nanoparticles are known to protect skin from ultraviolet rays (UVR) and delay photoaging. However, the photoprotective effects of these nanoparticles have not been broadly analyzed at a genetic level. The study objectives are as follows: (1) to investigate how UV-only and complete solar light can affect signaling pathways and genes related to photoaging in human dermal fibroblasts; (2) to investigate how TiO and ZnO nanoparticles provide photoprotection at a genetic level. RNAseq identified pathways and genes that were significantly affected by both irradiation conditions. Extracellular matrix (ECM) remodeling, inflammation, and cell cycle-related genes were subsequently validated by qPCR. The photoprotective properties of < 100 nm TiO and ZnO dispersions at a 25% active level were analyzed through quantitative differences in the irradiation-induced expression of these genes. There were < 15 signaling pathways affected by UV and complete solar light (p-value (-log10) > 1). Significant differences in gene expression following irradiation were found in MMP1, MMP3, PTGS1, PTGES, MDM2, CDKN1A, and CCNE2 (p ≤ 0.05) through qPCR. TiO and ZnO minimized the irradiation-induced expression of genes involved in the inhibition of matrix metalloproteinases, prostanoid biosynthesis, and cell cycle pathways. Photoprotection was best observed in cell cycle-related genes, showing expression differences of up to 74% (p ≤ 0.0001). However, no distinct differences in photoprotection between TiO and ZnO were found. The findings from this study serve as a framework for future optimization and development of inorganic sunscreen formulations to target genes that contribute to different aspects of skin aging.
已知无机纳米颗粒可保护皮肤免受紫外线（UVR）伤害并延缓光老化。然而，这些纳米颗粒的光保护作用尚未在基因水平上进行广泛分析。研究目标如下：（1）研究仅紫外线和完整太阳光如何影响人真皮成纤维细胞中与光老化相关的信号通路和基因；（2）研究二氧化钛（TiO）和氧化锌（ZnO）纳米颗粒如何在基因水平上提供光保护。RNA测序确定了受两种照射条件显著影响的信号通路和基因。随后通过定量聚合酶链反应（qPCR）验证了细胞外基质（ECM）重塑、炎症和细胞周期相关基因。通过这些基因照射诱导表达的定量差异，分析了活性水平为25%的<100 nm TiO和ZnO分散体的光保护性能。紫外线和完整太阳光影响了<15条信号通路（p值（-log10）>1）。通过qPCR发现在基质金属蛋白酶1（MMP1）、基质金属蛋白酶3（MMP3）、前列腺素内过氧化物合酶1（PTGS1）、前列腺素E合成酶（PTGES）、小鼠双微体2（MDM2）、细胞周期蛋白依赖性激酶抑制剂1A（CDKN1A）和细胞周期蛋白E2（CCNE2）中，照射后基因表达存在显著差异（p≤0.05）。TiO和ZnO使参与抑制基质金属蛋白酶、前列腺素生物合成和细胞周期通路的基因照射诱导表达最小化。在细胞周期相关基因中观察到最佳的光保护作用，表达差异高达74%（p≤0.0001）。然而，未发现TiO和ZnO在光保护方面有明显差异。本研究结果为未来优化和开发无机防晒配方以靶向导致皮肤老化不同方面的基因提供了框架。
