Measuring the toxicological ramifications of MNP exposure on skin senescence: Insights gained through network toxicology and transcriptomic analysis

Micro(nano) plastics (MNPs) are ubiquitous environmental pollutants with systemic toxicity to humans. As the primary barrier of the body, the skin is directly exposed to MNPs; however, the mechanisms underlying MNP-induced dermal toxicity remain unclear. Senescence-related functional assays were used to evaluate the senescent toxicity of polystyrene microplastics (MNP-PS). Next, we integrated network toxicology and transcriptomics to explore MNP toxicity in epidermal cells and multicellular analysis employed to identify MNP-senescence related targets. MNP-PS target 92 % (504/545) of MNP-associated genes. Cellular experiments, including β-galactosidase staining, reactive oxygen species (ROS) assay, and detection of Senescence-Associated Secretory Phenotype (SASP; IL-6, TNF-α, IL-1α), confirmed MNP-PS induces dose-dependent pro-senescent toxicity. The PPI network and transcriptomic analysis identified key functional modules linked to senescence toxicity: inflammation, cell cycle arrest, and oxidative stress. Integrative transcriptomic analysis across multicellular MNP exposure uncovered common potential targets: CXCL1, IL1R1, CDKN1A, JUN, and FOS. Our integrative analysis confirms MNP-PS-mediated pro-senescent toxicity, clarifies the mechanisms and key targets of its dermal toxicity, and highlights the utility of combining network toxicology and transcriptomics in toxicological research.