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Polyethylene terephthalate microplastics promote pulmonary fibrosis via AKT1, PIK3CD, and PIM1: A network toxicology and multi-omics analysis

Ecotoxicology and Environmental Safety 2025 5 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count. Score: 63 ? 0–100 AI score estimating relevance to the microplastics field. Papers below 30 are filtered from public browse.
Wenfei Zhao, Shanshan Yang, S.-J Hu, Yonghai Feng, Bing Bai

Summary

Using computational toxicology and multi-omics analysis, researchers identified three key proteins (AKT1, PIK3CD, and PIM1) through which PET microplastics may promote pulmonary fibrosis, a serious scarring disease of the lungs. The microplastics appear to affect metabolic and inflammatory pathways in specific lung and immune cells. This study provides molecular evidence for how inhaled plastic particles from everyday items could contribute to chronic lung disease.

Polyethylene terephthalate microplastics (PET-MPs) are persistent in the environment and have become an emerging health concern. PET-MPs play a role in lung pathologies; however, little is known about their role in idiopathic pulmonary fibrosis (IPF). Our research aimed to determine the role of PET-MPs in exacerbating IPF by combining improved detection and toxicology. The ProTox 3.0 platform was used to predict the microplastic toxicity of polyethylene terephthalate. The toxicological mechanism of PET-MP-induced IPF was explored using network toxicology, molecular docking, Mendelian randomization, and single-cell sequencing analysis. By analyzing the PubChem, ChEMBL, and SwissTargetPrediction databases, 120 potential targets related to PET-MPs exposure were identified, and 81 intersecting targets were obtained by intersecting the IPF gene in the Gene Expression Omnibus database. These were further optimized into three core targets, namely AKT1, PIM1, and PIK3CD. PET-MPs affected metabolic, lipid, atherosclerosis, and C-type selection receptor signaling pathways. The binding affinity of PET-MPs to these core targets was potent, and PET-MPs had a good binding effect with these target proteins. PET-MPs exhibit lung toxicity, which may be related to three key proteins: AKT1, PIK3CD, and PIM1. PET-MPs may exacerbate IPF via metabolic pathways, lipids, and atherosclerosis, which may occur in AT2 and CD8+T cells. This study offers valuable information on the molecular mechanism of IPF triggered by PET-MPs, emphasizing the practicality of network toxicology in the toxicity evaluation of emerging environmental contaminants.

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