Assessing the toxicological impact of PET-MPs exposure on IVDD: Insights from network toxicology and molecular docking.

Polyethylene terephthalate microplastics (PET-MPs) have emerged as a significant environmental concern due to their persistence and potential health hazards. Their role in degenerative diseases, particularly intervertebral disc degeneration (IVDD), remains poorly understood, highlighting the need for systematic evaluation of their molecular toxicity. In this study, network toxicology and molecular docking approaches were applied to investigate the toxicological mechanisms of PET-MPs-induced IVDD. Comprehensive analyses of GEO, ChEMBL, STITCH, GeneCards, and OMIM databases identified 46 potential targets associated with PET-MPs exposure, which were further refined to seven core targets, including AKT1, CASP3, and SRC, using STRING and Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that PET-MPs influence immune-related pathways, such as Ras signaling, apoptosis, VEGF receptor signaling, and neutrophil extracellular trap (NET) formation. Molecular docking analysis confirmed strong binding affinities of PET-MPs to these core targets, suggesting its potential to disrupt key cellular processes. These findings indicate that PET-MPs may accelerate IVDD progression by modulating apoptosis, extracellular matrix (ECM) metabolism, angiogenesis, and immune responses. This study provides valuable insights into the molecular mechanisms underlying PET-MPs-induced IVDD and highlights the utility of network toxicology in evaluating the toxicity of emerging environmental pollutants, offering a theoretical foundation for understanding the health risks of PET-MPs and guiding strategies to mitigate their impact on degenerative diseases.