Polystyrene-associated pulmonary fibrosis: a summary based on the available evidence and prospects

Microplastics have become a pervasive component of the atmosphere and of indoor and occupational air, and the human respiratory tract is now recognized as a major and largely unavoidable route of exposure. Polystyrene, one of the most abundant commodity plastics, is a dominant model and real-world airborne microplastic, and mounting evidence links inhaled polystyrene microplastics (PS-MPs) to a spectrum of pulmonary injuries that increasingly implicate fibrogenesis. This review synthesizes the current mechanistic understanding of how PS-MPs may contribute to pulmonary fibrosis, drawing primarily on preclinical experimental evidence. We first outline the sources, physicochemical determinants and respiratory deposition behavior of airborne PS-MPs, and summarize the human, epidemiological and experimental evidence for pulmonary accumulation and harm. On the basis of converging but heterogeneous evidence we propose, as a working model rather than a validated cascade, that these upstream disruptions converge on a shared profibrotic signaling hub - coupled Wnt/ β -catenin and TGF- β 1/Smad2/3 signaling - that orchestrates epithelial-mesenchymal transition, myofibroblast differentiation and extracellular matrix remodeling, with epigenetic and ncRNA programs stabilizing the fibrotic phenotype. Because the elements of this model rest on different levels of evidence, we grade each of them explicitly as direct PS-MP pulmonary evidence, evidence extrapolated from other particles or toxicants, or canonical fibrosis biology. No study has yet tested the complete cascade, or the causal ordering of its modules, within a single PS-MPs inhalation model. Finally, we appraise candidate therapeutic strategies, including antioxidant and ferroptosis directed approaches and repurposing of approved antifibrotics. Meanwhile, we delineate the methodological limitations including nonphysiological doses, pristi5ne monodisperse particles and short exposure windows, that must be resolved before human respiratory risk can be quantified.