Transcriptional responses to real-world ambient air pollution in healthy and asthmatic human 3D airway models grown at the air-liquid interface

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Exposure to air pollution is a major risk factor for both acute and chronic respiratory diseases. This study aimed to analyze the transcriptomic changes in a human airway tissue model (MucilAir TM ), derived from healthy and asthmatic donors, cultured at the air-liquid interface. Samples were exposed for five days to ambient air under field conditions in three distinct Czech localities (background, industrial, urban) and differential expression of coding (mRNA) and non-coding (lncRNA and miRNA) RNAs was assessed. Whereas transcriptomic changes in samples exposed in the background and industrial localities were limited, urban ambient air induced marked RNA deregulation, particularly in healthy donor-derived samples, as reflected by higher numbers of downregulated mRNAs than in asthmatic samples (145 vs. 34 mRNAs, respectively). In healthy cells, the affected pathways included those associated with extracellular matrix organization, cell adhesion, proteoglycan-mediated growth factor binding, and downstream focal adhesion and PI3K-Akt signaling, suggesting modulation of structural and remodeling-related processes in response to pollution. In contrast, asthmatic donor-derived cells exhibited changes associated with altered epithelial function and stress-related responses. This was manifested by downregulation of expression of genes linked with epithelial homeostasis, secretory function, repair, proliferation, and immune communication, including SCGB3A1, CLCA2, GAL3ST4, CLSPN, GINS4, IL19 or CCL2 . Integrative analysis of miRNA-mRNA-lncRNA co-expression patterns further indicated distinct regulatory responses in both cell types. Overall, our findings suggest that air pollutants are associated with distinct epithelial transcriptional responses in healthy and asthmatic cells, providing new insight into the biological pathways and regulatory mechanisms involved in airway responses to air pollution.

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