Polystyrene nanoplastics-induced lung epithelial cells ferroptosis promotes pulmonary fibrosis via YY1/FTL axis

Nanoplastics (NPs) have emerged as pervasive environmental pollutants, and polystyrene nanoplastics (PS-NPs) have been increasingly implicated in pulmonary toxicity and fibrosis. Here, we established both an in vitro BEAS-2B bronchial epithelial injury model and an in vivo mouse model by repeated oropharyngeal aspiration of PS-NPs. We observed pronounced pulmonary fibrosis and ferroptotic death of alveolar type II cells. Integrated transcriptomic and proteomic profiling highlighted enrichment of the ferroptosis pathway, and in vitro and in vivo experiments confirmed that PS-NPs suppress GPX4 while inducing FTL, thereby driving lipid peroxidation. Mechanistically, YY1 binds the FTL promoter to repress its expression, and YY1 knockdown alleviates ferroptosis and fibrosis. Our findings identify YY1/FTL-mediated ferroptosis as a key mechanism by which PS-NPs induce pulmonary fibrosis.