Bisphenol A exacerbates diabetic foot ulcers through disruption of immune microenvironment and repair processes: a multi-omics analysis of environmental exposure mechanisms

Bisphenol A (BPA) impairs chronic wound healing via immune dysregulation, yet its mechanisms in diabetic foot ulcers (DFU) remain unclear. This study explores BPA's molecular mechanisms in DFU and screens for antagonists. BPA targets and DFU DEGs (from GEO) were intersected to identify common targets. PPI network construction, functional enrichment, and immune infiltration analyses were conducted. Single-cell sequencing and molecular docking validated target expression and BPA binding. Drug enrichment analysis predicted therapeutic compounds. A total of 51 common targets between BPA and DFU were screened. Functional enrichment analysis showed that these targets were mainly enriched in inflammatory responses, extracellular matrix remodeling, angiogenesis, and signaling pathways such as PI3K-Akt and MAPK. Three core targets were identified through network analysis: BCL2, EGFR, and MMP9. Single-cell analysis revealed that BCL2 was highly expressed in B cells, MMP9 was specifically expressed in macrophages, and EGFR was mainly expressed in fibroblasts and epithelial cells. Molecular docking confirmed that BPA had good binding activity with these three core targets (binding energy < -5.0 kcal/mol). Drug enrichment analysis screened multiple potential antagonists, including the marketed drugs enoxaparin and sulfasalazine. This study reveals BPA drives DFU via BCL2/EGFR/MMP9 targets, disrupting PPAR pathways and immune microenvironment, offering insights into pollutant-mediated wound healing and therapeutic targets for DFU.