Accumulation of polystyrene microplastics induces liver fibrosis by activating cGAS/STING pathway

Shen, Rong; Yang, Keren; Cheng, Xin; Guo, Changlei; Xing, Xiqing; Sun, Haonan; Liu, Disheng; Liu, Xiangwen; Wang, Degui

doi:10.1016/j.envpol.2022.118986

Cited by 99 publications

(56 citation statements)

References 48 publications

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“…Our finding was distinct from the study that 1 µm polystyrene MPs could enter planar cultured epithelial cells but not the nucleus region 16 , probably due to the difference between 3D and 2D cultivation. With prolonged exposure, 1 µm polystyrene MPs accumulated in N_DOs, consistent with in vitro/vivo studies showing that polystyrene MPs emerged and accumulated in human hepatocytes and animal livers 4,17 .…”

Section: Resultssupporting

confidence: 86%

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Liang

Luo

et al. 2022

Preprint

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The ubiquitous microplastics (MPs) and plastic additives in the environment usually form complexes, enter human blood circulation, and increase the risk of steatohepatitis. The liver Disse space plays a vital role in corresponding hepatic pathological processes. However, due to the limited understanding of the regulatory cues in multilineage maturation, the generation of large-scale Disse-like organoids (DOs) mirroring the comprehensive toxicity responses of MPs is challenging. Here, using human-induced pluripotent stem cells (hiPSCs), we biofabricated healthy donors and patient-derived DOs containing hepatocytes, endothelial cells, and hepatic stellate cells, resembling the features of Disse space. These organoids revealed that polystyrene MPs preferentially entered endothelial cells and then dispersed throughout the organoids, similar to reported studies in zebrafish. Co-exposure to MPs and tetrabromobisphenol A (TBBPA), a common plastic additive, showed enhanced accumulation of contamination in the organoids. We also biofabricated alcoholic liver disease (ALD) patient-derived DOs representing the specific disease transcriptional profiles. We found that co-exposure to MPs and TBBPA at environmental-related dosages significantly elevated the pathological transcriptional expression and biochemical profiles in patient-derived DOs but not in healthy organoids, suggesting that both hereditary factors and pollutants contribute to susceptibility to environmental toxicants. This study exemplified the value of biofabricated hiPSC-derived organoids in environmental toxicology and offered a powerful strategy for personalized toxicology evaluation.

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Section: Resultssupporting

confidence: 86%

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Liang

Luo

et al. 2022

Preprint

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“…In human beings, it has been found in different organs including the placenta [ 29 , 32 ]. Moreover, it has been shown that microplastic particles of 0.1 μm or less in size can enter hepatocytes from circulation and result in liver damage even at low concentrations [ 33 ]. Bonanomi et al found that carboxylate—modified polystyrene nanoparticles with an average size of 0.5 μm were internalized in CCD-18 human colon cells and led to metabolic changes [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Microplastic Contamination of Chicken Meat and Fish through Plastic Cutting Boards

Habib

Kindi

Salem

et al. 2022

IJERPH

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Microplastic contamination was found in fish and chicken bought on the market, in food stores and in chain supermarkets in the Middle East with the contamination ranging from 0.03 ± 0.04 to 1.19 ± 0.72 particles per gram of meat in chicken and from 0.014 ± 0.024 to 2.6 ± 2.8 particles per gram in fish. Only one fish was found to be free of microplastic. The source of the microplastic was established to be the polythene-based plastic cutting board the food was cut on. More microplastic contamination was found in food cut from the bone than in cut fillets when the fillets themselves were prepared on surfaces other than plastic. Washing the fish and chicken before food preparation decreased but did not completely remove the microplastic contamination. The fate of the microplastic in grilled fish was studied. The mechanical properties of typical plastic cutting boards commercially used in the markets were investigated in the form of tensile, hardness, and wear tests. Overall, the plastic cutting boards showed similar wear rates.

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“…and resulted in liver fibrosis. 4,5 Despite our recent study confirmed that this classical cGAS-STING signalling pathway is involved in liver fibrosis, 5 whether noncanonical cGAS-STING-PERK pathway also plays a vital role in liver fibrosis still remains to be elucidated. Inspired by the study of Zhang et al, 3 we tested the expression of cGAS-STING-PERK pathway in chronic CCl 4 exposure-driven fibrosis models.…”

mentioning

confidence: 85%

A non‐canonical cGAS‐STING‐PERK pathway may be involved in the pathogenesis of liver fibrosis

2022

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Accumulation of polystyrene microplastics induces liver fibrosis by activating cGAS/STING pathway

Cited by 99 publications

References 48 publications

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Toxicity of microplastics and plastic additive co-exposure in liver Disse organoids from healthy donors and patient-derived induced pluripotent stem cells

Microplastic Contamination of Chicken Meat and Fish through Plastic Cutting Boards

A non‐canonical cGAS‐STING‐PERK pathway may be involved in the pathogenesis of liver fibrosis

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