With the increasing consumption of plastic products, microplastics (MPs) and nanoplastics (NPs), as new environmental pollution, pose a huge potential threat to human health. The different polymers and sizes of MPs and NPs are important factors determining the distribution and pathways of particulate organisms, thereby affecting their toxicity. The study explored the pulmonary toxicity and potential mechanism of MPs (1 μm) and NPs (100 nm) of polystyrene (PS), polyethylene (PE), or polypropylene (PP) in vivo and in vitro. Intratracheal injection of MPs/NPs (10 mg/kg, once every six days, continued four times) in mice induced pulmonary histopathological changes, raised α-SMA and collagen I expressions, the TIMP-1/MMP13 ratio, epithelial-mesenchymal transition (EMT)-related proteins, recruited immune cells and increased pro-inflammatory cytokine secretion, especially in PS-NPs group. MPs/NPs (PS, PE or PP) exhibited cytotoxicity in human lung epithelial BEAS-2B, and MPs/NPs (50 μg/mL, 8 h) up-regulated α-SMA, Vimentin, and IL-1β expressions. PS-NPs raised YAP1 and inhibited FXR expression in mice or BEAS-2B, compared with other polymers or diameters. In PS-NPs-induced BEAS-2B, Verteporfin (YAP1 antagonist, 0.2 μM) or GW4064 (FXR agonist, 2 μM) reduced α-SMA, Vimentin, and IL-1β expressions, while Gugglesterone (FXR antagonist, 50 μM) increased above protein expressions. Meanwhile, FXR deficiency increased YAP1 activity and fibrogenesis in PS-NPs-induced BEAS-2B. Collectively, MPs/NPs exposure elevates the risk of pulmonary fibrosis, and FXR-YAP1 axis dysregulation may underlie their toxicity mechanisms. Among the tested polymers, PS exhibits stronger pulmonary toxicity and cytotoxicity compared to PE or PP, and NPs of the same polymer demonstrate greater pulmonary toxicity than MPs.
