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Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models

ABSTRACT: Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models

PROVIDER: PRJNA1202138 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR31810124_1.fastq.gz	Fastqsanger.gz
	SRR31810124_2.fastq.gz	Fastqsanger.gz
	SRR31810126_1.fastq.gz	Fastqsanger.gz
	SRR31810126_2.fastq.gz	Fastqsanger.gz

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Project description:Micro and nanoplastics (MNPs) are widespread contaminants of our environment and food web that can be absorbed by the intestine and distributed to most or all organs, and may cause significant toxicity and dysfunction. In our recent study, we investigated the toxicity and mechanisms underlying uptake and translocation of 26 nm carboxylated polystyrene MNPs (PS26C) using a combination of simulated digestion and a static, immortalized cell-based, three cell type (triculture) small intestinal epithelial model. Results revealed that PS26 caused minimal toxicity, and inhibitor studies revealed that uptake mechanisms included passive diffusion, phagocytosis, clathrin-mediated endocytosis (CME), and fast endophilin-mediated endocytosis (FEME). However, the triculture model is somewhat lacking in physiological relevance, and studies in a more relevant and accurate model are required to validate and expand upon those results. In the current study, we therefore employed a microfluidic intestine-on-a-chip model developed using primary human intestinal epithelial organoids from both healthy and Crohn’s disease donors, and primary human microvascular endothelial cells to evaluate the toxicological impacts and mechanisms effectuating uptake and translocation of 25 nm polystyrene shell-gold core tracer (quantifiable by ICP-MS) MNPs (AuPS25). As in our previous study, AuPS25 caused minimal toxicity after 24 h exposure in either the healthy or Crohn’s IOC model. RNAseq analysis of epithelial cell lysates identified only 9 dysregulated genes, which notably included downregulation of IFI6 (interferon alpha-induced protein 6), which has antiviral and negative innate immune regulatory functions in the intestine. Inhibitor studies revealed that AuPS25 uptake occurred by both passive and active mechanisms, including phagocytosis and/or macropinocytosis, and CME and/or FEME. Interestingly, uptake and translocation of AuPS25 was greater in healthy than in unstimulated Crohn’s disease epithelium.

Project description:Micro- and nanoplastics (MNPLs) have emerged as pervasive environmental pollutants, raising growing concerns about their potential health risks. Their documented presence in the human bloodstream highlights the need to understand their interactions with endothelial cells and their role in cardiovascular diseases such as atherosclerosis. However, the full implications of these interactions remain largely unknown. To address this, we investigated the impact of three sizes (30, 50, and 100 nm) of polystyrene carboxylated nanoplastics (PS-C-NPLs) on human umbilical vein endothelial cells (HUVECs) at 100 µg/mL. By integrating in vitro assays with bioinformatic transcriptomic analyses, we employed a multimodal approach to comprehensively investigate the effects of PS-C-NPLs on endothelial cells. In vitro assessments included nanoplastics (NPLs) internalisation (flow cytometry, confocal microscopy, TEM), morphological and internal complexity changes (flow cytometry), genotoxicity (comet assay), and functional alterations, such as cholesterol biosynthesis (Filipin III staining), migration (wound healing assay), angiogenesis, and inflammation (IL-6 ELISA). Additionally, RNA sequencing provided transcriptomic insights into the cellular response to PS-C-NPLs, complementing the in vitro findings and revealing molecular pathways underlying the observed effects. All three PS-C-NPL sizes were rapidly internalised by HUVECs within 20 minutes, inducing significant alterations in cell morphology, internal complexity, and function. PS-C-NPLs caused genotoxic damage and disrupted cholesterol metabolism, migration, angiogenesis, and inflammatory responses. Notably, some effects exhibited a size-dependent trend, with similarities emerging between carboxylated polystyrene (PS-C) 50 and 100 nm NPLs, while the smallest 30 nm NPL showed slightly distinct responses. Transcriptomic analyses reinforced these findings, revealing shared pathways across all three PS-C-NPLs —linked to cholesterol metabolism, endothelial-to-mesenchymal transition, DNA damage, and inflammation — alongside size-specific molecular signatures. This study is the first to comprehensively link transcriptomic changes to size-dependent functional alterations in endothelial cells induced by PS-C-NPLs. Our findings demonstrate that PS-C-NPLs significantly impair endothelial cell function and integrity in a size-dependent manner, underscoring their potential cardiovascular risks.

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Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models

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