Identification of Core targets and Signaling pathways in Bisphenol A-mediated atopic dermatitis: an integrative network toxicology, cell-based, and In vivo validation study

Abstract Atopic dermatitis (ad) is a chronic inflammatory skin disease characterized by xerosis, eczematous lesions, and intense pruritus. Bisphenol A (BPA), a ubiquitous endocrine disruptor, impairs immune function and promotes cutaneous inflammation, yet its precise role in ad pathogenesis remains unclear. This study integrated network toxicology, molecular docking, HaCaT cell experiments, and a DNCB-induced mouse model with oral BPA exposure to systematically investigate BPA-induced ad mechanisms. Venn analysis identified 94 shared BPA-ad targets, and PPI network analysis selected five core targets (TNF, CXCL8, MMP9, TP53, PTGS2). Functional enrichment highlighted inflammatory/immune processes and the NF-κB pathway. Molecular docking confirmed stable BPA binding to all five targets, with PTGS2 showing the strongest affinity. In HaCaT cells, BPA dose-dependently reduced viability, increased TNF-α and CXCL8 secretion, and upregulated MMP9, PTGS2, and phosphorylated NF-κB. In vivo, BPA exposure exacerbated DNCB-induced ear lesions, epidermal hyperplasia, and serum TNF-α and IL-6 levels. GEO clinical dataset analysis further supported translational relevance. These findings provide a theoretical basis for understanding BPA-induced ad mechanisms and identify candidate targets for environmental risk management and targeted intervention in ad.