Polystyrene microplastics-induced macrophage extracellular traps contributes to liver fibrotic injury by activating ROS/TGF-β/Smad2/3 signaling axis

• Published in: Environmental pollution (1987) Vol. 324; p. 121388
• Main Authors: Wang, Shengchen, Chen, Lu, Shi, Xu, Wang, Yue, Xu, Shiwen
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2023
• Subjects: Animals; Cell co-culture; Epithelial-mesenchymal transition; Extracellular Traps; Humans; Liver - metabolism; Liver fibrosis; Macrophage extracellular traps; Mice; Microplastics; Microplastics - metabolism; Microplastics - toxicity; Plastics; Polystyrenes - metabolism; Polystyrenes - toxicity; Reactive Oxygen Species; Smad2 Protein; Epithelial-mesenchymal transition; Macrophage extracellular traps; Microplastics; Liver fibrosis; Cell co-culture
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2023.121388

Microplastics (MPs) are a type of emerging pollutant, posing a great threat to human and animal health. While recent studies have revealed the link between MPs exposure and liver injury of organisms, the effect of particle size on the level of MPs-induced hepatotoxicity and the intrinsic mechanism remain to be explored. Here, we established a mouse model exposed to two-diameter polystyrene MPs (PS-MPs, 1–10 μm or 50–100 μm) for 30 days. The in vivo results revealed that PS-MPs caused liver fibrotic injury in mice, accompanied with macrophages recruitment and macrophage extracellular traps (METs) formation, which were negatively correlated with particle size. The data in vitro showed that PS-MPs treatment could induce macrophages to release METs in a reactive oxygen species (ROS)-independent manner, and the METs formation level caused by large-size particles was higher than small-size particles. Further mechanistic analysis of a cell co-culture system revealed that PS-MPs-induced METs release led to a hepatocellular inflammatory response and epithelial-mesenchymal transition (EMT) via activating the ROS/TGF-β/Smad2/3 signaling axis, and this biological crosstalk could be relieved by DNase I. Overall, this findings demonstrates the key role of the action mechanism of METs in aggravating MPs-caused liver injury. [Display omitted] •1–10 μm PS-MPs exposure caused more severe liver fibrosis than 50–100 μm PS-MPs.•PS-MPs induced METosis formation to aggravate liver fibrosis.•50–100 μm PS-MPs stimulation induced more METs release than 1–10 μm PS-MPs.•PS-MPs-induced METosis activated hepatocellular EMT and inflammatory response.•PS-MPs-induced METosis activated hepatocellular ROS/TGF-β/Smad2/3 axis.