Unraveling the mechanisms of bisphenol A-Induced lupus nephritis through network toxicology and machine learning approaches.

Journal: International journal of environmental health research
Published Date: Aug 21, 2025

Abstract

This study aimed to identify the potential toxic targets and molecular mechanisms underlying bisphenol A (BPA) exposure-induced lupus nephritis (LN) using network toxicology and machine learning. By leveraging the online databases SwissTargetPrediction, ChEMBL, STITCH, GeneCards, and OMIM, we identified 94 potential targets associated with BPA and LN. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, conducted using the Metascape database, revealed that the core targets associated with BPA's effects on lupus nephritis were significantly enriched in several key pathways, including apoptosis, MAPK signaling, toll-like receptor signaling, estrogen signaling, and NF-κB signaling. In addition, three machine learning algorithms, LASSO regression, SVM-RFE, and random forest (RF), were used for cross-validation and screening of core genes, and five key target genes were identified, including JUN, CYP3A4, PLAU, PTGS2, and NOTCH1. Molecular docking experiments using AutoDock confirmed the potential interactions between BPA and these core targets. In conclusion, these findings suggest that BPA may induce lupus nephritis by modulating key pathways, including apoptosis, MAPK signaling, Toll-like receptor signaling, estrogen signaling, and NF-κB signaling. This study demonstrates that BPA exposure can act as an environmental trigger in the development of LN.

Authors

  • Zhongfu Tang
    Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
  • Ming Li
    Radiology Department, Huadong Hospital, Affiliated with Fudan University, Shanghai, China.
  • Lili Cheng
    Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China.
  • Junjie Chen
    College of Computer Science and Technology, Taiyuan University of Technology, Taiyuan, China.
  • Chuanbing Huang
    Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.

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