Integrative bioinformatics analysis reveals that microplastics promote chronic rhinosinusitis with nasal polyps through NOXO1-mediated oxidative stress and myoepithelial cell reprogramming.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease whose environmental pathogenic factors remain unclear. Microplastics, as emerging environmental pollutants, have been confirmed to deposit in the respiratory tract and induce inflammatory responses; however, their molecular association with CRSwNP pathogenesis remains elusive. This study integrates transcriptomic data from microplastic-exposed human airway epithelial cells and single-cell transcriptomic data from CRSwNP patients, employing machine learning algorithms to screen core genes and systematically exploring disease mechanisms through single-cell analysis, pseudotime trajectory inference, cell-cell communication analysis, and transcriptional regulatory network analysis. The study identified 29 genes commonly upregulated in both microplastic exposure and CRSwNP, with NOXO1 being consistently identified as the core driver gene by all algorithms. Single-cell analysis revealed that myoepithelial cells exhibited specific high responsiveness to microplastic-related genes and showed significantly increased proportions in CRSwNP. Pseudotime analysis unveiled aberrant differentiation trajectories involving myoepithelial cells and basal cells, characterized by high expression of CCL20, CNN1, and MXRA5. Cell-cell communication analysis identified pathological crosstalk between myoepithelial cells and mast cells through the LAMB3-CD44 axis, while SCENIC analysis demonstrated significant activation of EMT-related transcription factors (TWIST1/2, SOX18) in myoepithelial cells. This study establishes for the first time a molecular mechanistic model of microplastic-induced CRSwNP: microplastics trigger oxidative stress by upregulating NOXO1, driving pathological reprogramming of myoepithelial cells, establishing inflammatory amplification loops with mast cells through the LAMB3-CD44 axis, and ultimately promoting polyp formation. These findings provide novel insights into the role of environmental factors in CRSwNP pathogenesis and identify potential therapeutic targets.