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Polystyrene nanoplastics exacerbate dibutyl phthalate-induced liver fibrosis through PDGFRα-dependent hepatic stellate cell activation
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Researchers found that polystyrene nanoplastics worsen liver fibrosis caused by dibutyl phthalate, a common plasticizer, through activation of hepatic stellate cells via the PDGFRalpha signaling pathway. The study suggests that nanoplastics act as environmental carriers that facilitate cellular uptake of harmful plasticizers, amplifying their toxic effects on liver tissue.
Nanoplastic particles (NPs) derived from common polymers such as polyvinyl chloride and polystyrene (PS) act as persistent environmental reservoirs that facilitate the transport and cellular internalization of dibutyl phthalate (DBP), a ubiquitous plasticizer contaminating air, water, soil, and food through plastic leaching. The platelet-derived growth factor receptor α (PDGFRα) pathway is a well-established regulator of hepatic stellate cell (HSC) activation and fibrogenesis; however, its mechanistic involvement in plastic particle-induced hepatotoxicity and its intersection with DBP-mediated fibrosis remain unclear. Using HSC-hepatic cell cocultures (LX-2-HepG2 or LO2) and transcriptomic profiling, we demonstrate that DBP exposure markedly decreases hepatic cellular viability, elevates proinflammatory cytokines (TNF and IL-6), and induces apoptosis. In parallel, DBP stimulates LX-2 proliferation and upregulates fibrogenic markers (TGFB1, COL1A1, ACTA2) along with enhanced secretion of PDGF-A and PDGF-B, thereby reinforcing hepatic cell injury through paracrine signaling. RNA-seq analysis revealed activation of apoptotic and TNF-related pathways in LO2, whereas LX-2 cells exhibited upregulation of oncogenic and PI3K-Akt signaling, collectively promoting a profibrotic transcriptional landscape. In vivo, both PDGFRα antibody neutralization and pharmacological inhibition with imatinib significantly attenuated DBP-induced hepatic fibrosis and inflammatory gene expression, confirming PDGFRα's central role in DBP toxicity. Polystyrene nanoplastics (PS-NPs) were rapidly internalized by PDGFRα-positive primary HSCs within 24 h, leading to increased PDGFRα and PI3K expression. Co-exposure to PS-NPs and DBP resulted in synergistic hepatotoxicity and exacerbated fibrotic injury, demonstrating compounding effects of mixed environmental pollutants. Collectively, these findings identify PDGFRα as a mechanistic nexus linking DBP and PS-NPs exposure to hepatic fibrosis and highlight its potential as a therapeutic target for environmentally induced liver disease. The results further underscore the importance of co-exposure paradigms in evaluating the health risks of complex contaminant mixtures.
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Polystyrene Nanoplastics Exacerbate CCl4-Induced Liver Fibrosis by Aggravating Stretch-Induced Mechanical Stress in Hepatic Stellate Cells
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Researchers found that chronic exposure to polystyrene nanoplastics worsens chemical-induced liver fibrosis in mice by directly activating hepatic stellate cells through a stretch-induced mechanical stress pathway involving the TGF-β receptor, independent of macrophage-mediated inflammation.
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Researchers found that polystyrene nanoplastics worsened liver damage in mice fed a high-fat diet by increasing oxidative stress, inflammation, and the infiltration of immune cells in liver tissue. The nanoplastic exposure accelerated the progression from fatty liver to hepatic fibrosis in the diet-induced model. The study suggests that nanoplastic exposure may compound the health risks associated with metabolic conditions affecting the liver.
Polystyrene microplastics and hepatic fibrosis-related indices in type 2 diabetes: a cross-sectional analysis with experimental validation
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Researchers found that polystyrene microplastics detected in blood were the polymer most consistently linked to elevated liver fibrosis markers in type 2 diabetic patients, and confirmed in diabetic mice that PS-MPs worsen hepatic steatosis and fibrosis by activating the NLRP3 inflammasome and TGF-β1/Smad signaling pathways.
Polystyrene nanoplastics exacerbated Pb-induced liver toxicity in mice
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Researchers found that polystyrene nanoplastics exacerbated lead-induced liver toxicity in mice, with co-exposure causing higher lead accumulation, more severe inflammation, increased oxidative stress, and greater disruption of protective Nrf2 signaling pathways compared to lead alone.
Accumulation of polystyrene microplastics induces liver fibrosis by activating cGAS/STING pathway
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Researchers found that tiny polystyrene microplastics (0.1 micrometers) can enter liver cells and cause DNA damage that triggers a chain reaction leading to liver scarring, known as fibrosis. The microplastics activated a specific immune signaling pathway called cGAS/STING, which caused inflammation that progressively damaged liver tissue even at low concentrations. This study reveals a specific mechanism by which long-term microplastic exposure could lead to serious liver disease in humans.
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