Measuring the toxicological ramifications of MNP exposure on skin senescence: Insights gained through network...

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.