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Article ? AI-assigned paper type based on the abstract. Classification may not be perfect — flag errors using the feedback button. Tier 2 ? Original research — experimental, observational, or case-control study. Direct primary evidence. Environmental Sources Nanoplastics Sign in to save

Inhibition of iron ion accumulation alleviates polystyrene nanoplastics-induced pulmonary fibroblast proliferation and activation

International Immunopharmacology 2025 7 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Demin Cheng, Demin Cheng, Dongnan Zheng, Mengna Jiang, Mengna Jiang, Yan Jin, Yan Jin, Rongzhu Liu, Yifan Zhou, Jinping Shen, Jinyu Tang, Fengxu Wang, Juan Tang, Shan Bao, Jinlong Li, Hong Chen, Xinyuan Zhao

Summary

Researchers found that polystyrene nanoplastics (80 nm) caused lung cells to transform into scar-forming cells, a process that leads to pulmonary fibrosis, a serious and often irreversible lung disease. The key mechanism involved iron buildup in lung cells, which was triggered by interactions between immune cells and the nanoplastics. Importantly, blocking iron accumulation with an existing medication reversed the harmful effects, suggesting a potential treatment approach for nanoplastic-related lung damage.

Polymers
Models
Study Type In vivo

Microplastics (MPs) and nanoplastics (NPs) are increasingly recognized as widespread environmental pollutants with significant ecological and human health implications, with particularly severe impacts on the respiratory system. This study aimed to explore the effects of polystyrene nanoplastics (PS-NPs, 80 nm) on pulmonary fibroblast proliferation and activation in NIH/3 T3 cells. Herein, we conducted a PS-NPs-induced fibroblast-to-myofibroblast transition (FMT) model and a pulmonary fibrosis mouse model. We found that PS-NPs effectively promoted fibroblast activation, proliferation, migration, and contraction. Fibroblast transcriptomics analyses revealed the enrichment of pathways involved in mineral absorption, mainly involved in iron ions, after PS-NPs treatment. Mechanistically, the elevated level of Fe in PS-NPs-stimulated NIH/3 T3 cells originated primarily from macrophages and epithelial cells, as validated by co-culture systems of fibroblasts with epithelial cells and fibroblasts with macrophages. Moreover, treatment with the iron chelator DFO and the mineral absorption pathway inhibitor Esomeprazole (a classic proton pump inhibitor, PPI) significantly reduced fibroblast activation. Consistent with the in vitro findings, in vivo results supported the occurrence of pulmonary fibrosis following PS-NPs exposure, accompanied by increased iron content in lung tissues. Collectively, these results revealed that PS-NPs could promote fibroblast activation and pulmonary fibrosis by augmenting intracellular iron content through enhancing epithelial-fibroblast and macrophage-fibroblast cross-talk. Therefore, our study also suggested that targeting intercellular crosstalk and iron homeostasis might be a promising therapeutic strategy for PS-NPs-induced pulmonary fibrosis.

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