Bisphenol A drives acne pathogenesis by disrupting immune homeostasis: an integrated in silico and clinical transcriptomics study

Abstract

This study aimed to elucidate the toxic mechanism by which bisphenol A (BPA) exacerbates acne pathogenesis from an ecotoxicological perspective. We identified 55 potential toxic targets of BPA and conducted network analysis, which revealed five core hub genes: MMP9, INS, ESR1, BCL2, and CXCL8. Validation with clinical samples demonstrated that MMP9 and CXCL8 were significantly upregulated in acne lesions. Conversely, ESR1 was downregulated, indicating their potential as diagnostic biomarkers. In contrast, BCL2 and INS did not show significant expression alterations. Acne pathogenesis was found to be critically driven by CXCL8 and MMP9, two genes that ranked at the vanguard of hub genes as delineated through machine learning analysis. Molecular docking and molecular dynamics (MD) simulations suggested a potentially stable interaction between BPA and these core target proteins. In vitro experiments demonstrated that BPA increased lipid droplet formation while upregulating CXCL8 and MMP9 expression in sebaceous gland cells. Further bioinformatic analysis revealed that these hub genes critically modulate the infiltration of neutrophils, macrophages, and T cells. This modulation disrupts skin immune homeostasis and drives the inflammatory progression of acne. Our findings demonstrate that environmental exposure to BPA increases acne susceptibility by targeting key regulatory genes and disturbing the local immune microenvironment. This work provides a mechanistic framework for evaluating the cutaneous ecotoxicity of BPA. Additionally, the established computational strategy offers a rapid, cost-effective, and ethically feasible approach for assessing the hazards of environmental pollutants. This supports environmental safety control and public health initiatives aimed at preventing pollutant-associated skin diseases.