Although studies on the potential hepatotoxicity of nanoplastic depositions are being conducted, there remains a lack of research on the association between nanoplastic depositions and chronic liver disease. Therefore, this research aimed to explore the influence of polystyrene nanoparticles (PS-NPs) on the progression of liver fibrosis and the mechanisms involved in the hepatic stellate cells (HSCs) activation. Chronic exposure to PS-NPs aggravated CCl₄-induced liver fibrosis, as evidenced by enhanced collagen accumulation and elevated α-smooth muscle actin (α-SMA) expression. Most PS-NPs were accumulated in non-parenchymal liver cells, with Kupffer cells exhibiting the highest uptake. This accumulation was associated with enhanced recruitment of CD68-positive macrophages. However, PS-NPs were not associated with TGF-β expression in CD68-positive cells. Additionally, CD68-positive cells treated with PS-NPs did not affect α-SMA expression in HSCs. Further in vitro experiments revealed that α-SMA and pSmad2/3 were directly promoted by PS-NPs in both LX-2 HSCs and primary isolated HSCs, indicating a direct stimulatory effect on HSC activation. PS-NPs enhanced pTGFBR1 expression of HSCs by promoting stretch-induced mechanical stress, suggesting a novel pathway through which nanoplastics may exacerbate fibrogenesis. Our findings provide the first evidence that PS-NPs, as xenobiotic particles, can directly promote HSC activation and exacerbate liver fibrosis, indicating potential health risks associated with chronic nanoplastic exposure.

To Cite This Article: Yim JH, Kim TU, Kim WJ, Kim HY, Lee SW, Kang KK, Seo MS, Kim SD, Cho YE, Baek SM, Choi SK and Park JK, 2026. Polystyrene nanoplastics exacerbate CCl₄-induced liver fibrosis by aggravating stretch-induced mechanical stress in hepatic stellate cells. Pak Vet J, 46(3): 544-555. http://dx.doi.org/10.29261/pakvetj/2026.043