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Inhalable textile microplastic fibers impair airway epithelial differentiation

ABSTRACT: Rationale Microplastics are a pressing global concern and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives Our aim was to assess the effects of 12x31 µm nylon 6,6 (nylon) and 15x52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate and 7 days later organoid-forming capacity of isolated epithelial cells was investigated. Results We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate, also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects were recapitulated in human air-liquid interface cultures. Transcriptome analysis revealed upregulation of Hoxa5 post-exposure to nylon fibers. Inhibiting Hoxa5 protein during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair and we strongly encourage to characterize both hazard of and exposure to microplastic fibers in more detail.

ORGANISM(S): Mus musculus

PROVIDER: GSE238065 | GEO | 2023/12/31

REPOSITORIES: GEO

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Project description:Airway organoids derived from adult murine epithelial cells represent a complex 3D in vitro system mimicking the airway epithelial tissue’s native cell composition and physiological properties. In combination with a precise damage induction via femtosecond laser-based nanosurgery, this model allows for the examination of intra- and intercellular dynamics in the course of repair processes with a high spatio-temporal resolution, which can hardly be reached using in vivo approaches. For characterization of the organoids’ response to single or multiple-cell ablation, we first analyzed overall organoid survival and found that airway organoids were capable of efficiently repairing damage induced by femtosecond laser-based ablation of a single to ten cells within 24 h. An EdU staining assay further revealed a steady proliferative potential of airway organoid cells. Especially in the case of ablation of five cells, proliferation was enhanced within the first four hours upon damage induction, whereas ablation of ten cells was followed by a slight decrease in proliferation within this time frame. Analyzing individual trajectories of single cells within airway organoids, we found an increased migratory behavior in cells within close proximity to the ablation site following the ablation of ten, but not five cells. Bulk RNA sequencing and subsequent enrichment analysis revealed the differential expression of sets of genes involved in the regulation of epithelial repair, distinct signaling pathway activities such as Notch signaling, as well as cell migration after laser-based ablation. Together, our findings demonstrate that organoid repair upon ablation of ten cells involves the same key processes by which native airway epithelial wound healing is regulated. This marks the herein presented in vitro damage model suitable to study repair processes following acute airway injury, thereby posing a novel approach to gain insights into the mechanisms driving epithelial repair on a single-cell level.

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Inhalable textile microplastic fibers impair airway epithelial differentiation

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