Analysis of the effects of perfluorooctane sulfonate on COPD using network toxicology and molecular docking

This study elucidates the pathogenic mechanisms of perfluorooctane sulfonate (PFOS) in chronic obstructive pulmonary disease (COPD) through network toxicology and molecular docking. By integrating multiple databases, we identified 158 PFOS-related targets in COPD, with five key proteins (epidermal growth factor receptor [EGFR], ESR1, GRB2, HSP90AA1, and SRC) showing central roles in protein interaction networks. Functional enrichment analysis revealed their involvement in key pathophysiological processes, including airway inflammatory responses, oxidative stress, and immune regulation, primarily through modulation of cell survival and proliferation pathways and immune and hormonal regulation pathways. Gene set enrichment analysis (GSEA) further validated these findings by confirming the significant enrichment of five key KEGG pathways identified in our analysis. Molecular docking studies confirmed high-affinity binding between PFOS and these core targets, indicating PFOS may dysregulate inflammatory responses, oxidative balance, and cellular proliferation in COPD pathogenesis. These findings provide critical molecular insights into environmental pollutant-aggravated respiratory disorders and highlight potential intervention targets for COPD management.