Precision environmental medicine: Integrated multi-exposure transcriptomics for shared molecular networks in COPD pathogenesis in response to environmental exposure
PRECISION MEDICAL SCIENCES, 2026 (ESCI)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/prm2.70037
- Dergi Adı: PRECISION MEDICAL SCIENCES
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI)
- Kocaeli Üniversitesi Adresli: Evet
Özet
Smoking, ozone, and fine particulate matter (PM2.5) provoke simultaneous chemical reactions that damage and irritate the lungs, leading to chronic obstructive pulmonary disease (COPD). The fundamental biological mechanisms are ambiguous, hindering the advancement of treatment alternatives. We performed a comprehensive systems-biology study of 2847 genes associated with these three primary environmental exposures to investigate these pathways. We used differential gene expression analysis of exposure-specific transcriptomic datasets and advanced computational methods, including pathway overrepresentation analysis, protein interaction network construction, and computational drug repurposing. A fundamental set of 647 genes was recognized as dysregulated across all three exposure categories. Research on network centrality identified cytochrome P450 1B1 (CYP1B1) as a hub gene (betweenness centrality = 0.94), underscoring its regulatory function. CYP1B1 plays a crucial function in integrating xenobiotic signals via the AhR, linking metabolic activities to subsequent inflammatory and oxidative stress pathways. We identified three dominant pathways: TNF-alpha/NF-kappa B signaling (false discovery rate [FDR] = 1.2 & times; 10-15 to 4.3 & times; 10-18), oxidative stress response (FDR = 2.1 & times; 10-18 to 8.9 & times; 10-16), and xenobiotic metabolism (FDR = 1.8 & times; 10-25 to 3.4 & times; 10-30). Our network analysis reveals a highly interconnected regulatory module in which CYP1B1 directly modulates NF-kappa B activity, indicating that xenobiotic metabolism activates the inflammatory response. A thorough regulatory network model identified 187 genes critical for this conserved response. Computational drug repurposing found 15 candidate activators of the NRF2 pathway and inhibitors of cytokine signaling that target these interrelated pathways. A network-proximity-based approach discovered medicines with markedly improved targeting within core network modules. Key options for inflammatory respiratory illnesses are NRF2 pathway activators, such as sulforaphane, and cytokine signaling inhibitors, such as tocilizumab. This article clarifies the molecular structure behind environmentally induced COPD pathogenesis, with an emphasis on CYP1B 1. Irrespective of initial exposure, the essential pathways and revised therapeutic choices establish a basis for accurate, preventive, and mechanism-oriented therapies designed to mitigate environmentally generated respiratory illnesses.