Benzo[a]pyrene and Rheumatoid Arthritis: An Integrated Computational Investigation

Area of Science:

• Environmental toxicology
• Computational biology
• Rheumatology

Background:

• Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants linked to rheumatoid arthritis (RA) pathogenesis.
• Benzo[a]pyrene (BaP), a prominent PAH, is suspected to contribute to RA onset, but its toxicological mechanisms require elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms underlying Benzo[a]pyrene's potential role in rheumatoid arthritis development.
• To identify key genes and pathways affected by BaP exposure in the context of RA.

Main Methods:

• Integrated network toxicology, machine learning, and molecular docking approaches.
• Identification and network construction of BaP's RA-related target genes.
• Gene Ontology (GO) and KEGG pathway enrichment analyses.
• Topological analysis and machine learning for core gene identification.
• Molecular docking and dynamics simulations to assess binding affinity.

Main Results:

• Fifteen potential RA-related target genes of BaP were identified, enriched in leukocyte migration and immune signaling pathways (e.g., NF-κB, T cell receptor).
• Five core genes (LCK, ZAP70, ITK, GZMA, ITGAL) were identified and validated.
• BaP demonstrated strong binding affinity to the protein products of these core genes, forming stable complexes.

Conclusions:

• This study provides a computational framework elucidating BaP's potential mechanisms in RA pathogenesis.
• Findings offer a theoretical basis for understanding RA development linked to environmental pollutants like BaP.
• Highlights potential therapeutic targets for RA prevention and treatment.