Abstract
Micro- and nanoplastics (MNPs) are emerging pollutants that can carry harmful substances like benzo(a)pyrene, posing potential health risks. While the harmful effects of nanoplastics on the lungs are known, how they interact with benzo(a)pyrene to affect cellular communication remains unclear. In our study, We explore this interplay using a 16-week mouse model exposed to environmentally relevant doses of polystyrene nanoplastics, benzo(a)pyrene, or a combination of both. We find that only the combined exposure leads to significant lung damage, characterized by severe inflammation and tissue scarring, which are not seen with single exposures. This combined exposure also increases oxidative stress and reduces antioxidant defenses in the lungs. Furthermore, we notice increased levels of inflammation-related molecules and markers of lung tissue damage, confirming a more severe toxic effect. Transcriptomic analysis highlights the involvement of the Relaxin signaling pathway, which influences inflammatory and tissue damage processes through PI3K-AKT and MAPK cascades; Relaxin4 activated PLC-IP3R, opening ER calcium channels and raising cytosolic Ca²⁺, which triggered macrophage extracellular trap (MET) formation. Additionally, a macrophage-MLE-12 co-culture system confirmed that Mix-induced METs are linked to the exacerbation of alveolar inflammation and the progression of pulmonary fibrosis. Our findings reveal novel molecular connections that explain how these pollutants worsen lung health, suggesting that targeting the identified signaling pathways could offer a potential approach to mitigating these harmful effects.
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Data availability
All data supporting the findings are included in the paper and its supplementary files. All raw data are provided in the supplementary information. Sequencing reads are deposited in NCBI SRA under accession PRJNA1401317. Additional data are available from the corresponding author upon reasonable request.
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Acknowledgements
This work was supported by the Major Science and Technology plan of Hainan Province (ZDYF2022SHFZ321), National Natural Science Foundation of China (42377273), Research start-up Project of Hainan University (XJ2300009832), Hainan Provincial Graduate Innovation Research Project (SA2400003272).Hainan Province Science and Technology Special Fund (ZDYF2022SHFZ321). We would like to express our gratitude to the Biorender website (https://app.biorender.com/) for providing resources for creating illustrations.
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Yu Chen: Conceptualization, Writing-Original Draft, Formal analysis, Data Curation, Methodology, Data Curation, Yingai Zhang: Project administration, Resources. Yuting Zhang: Methodology. Xu Zhang: Data Curation. Shuguo Lv: Revision, Resource. Mohamed Mohsen: Methodology, Writing - Review & Editing. Kai Yin : Supervision, Methodology. Xiaoshan Zhu: Resource. Hailong Zhou: Supervision, Funding acquisition.
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Chen, Y., Zhang, Y., Zhang, Y. et al. Polystyrene nanoplastics and benzo(a)pyrene synergistically induce lung fibrosis and inflammation via relaxin signalling in mice. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09872-9
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DOI: https://doi.org/10.1038/s42003-026-09872-9
