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Environmental nitro-aromatic compounds link pulmonary fibrosis through BCL2L1 structural destabilization
Hanming Yu1, Miao Li2, Xin Kang1
1Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Ecotoxicology and Environmental Safety
|July 27, 2026
Summary
Environmental nitro-aromatic compounds (NACs) disrupt the structural stability of the BCL2L1 protein, contributing to pulmonary fibrosis progression and altering the immune microenvironment. This suggests BCL2L1 structural toxicity as a target for pollution-related lung fibrosis.
Area of Science:
- Environmental toxicology
- Molecular biology
- Computational toxicology
Background:
- Nitro-aromatic compounds (NACs) are widespread environmental pollutants known for pulmonary toxicity.
- The precise mechanisms by which NACs contribute to pulmonary fibrosis are not fully understood.
Purpose of the Study:
- To investigate the fibrogenic effects of representative NACs, 1-nitropyrene (1-NP) and nitrobenzene (NB).
- To identify NACs-related molecular targets and assess their clinical relevance in idiopathic pulmonary fibrosis (IPF).
Main Methods:
- Integrative framework combining network toxicology, transcriptomics, prognostic modeling, immune profiling, molecular docking, and molecular dynamics (MD) simulations.
- Analysis of the IPF GEO dataset to evaluate NACs-related targets.
Main Results:
- Ten key genes were identified in the NACs-associated fibrosis network, with BCL2L1 and MYC showing prognostic significance in IPF.
- NACs (1-NP, NB) bind to BCL2L1, causing structural destabilization and partial unfolding, indicating a mechanism of structural toxicity.
- Risk models based on hub genes correlated with immune dysregulation, including macrophage aggregation and T cell exhaustion.
Conclusions:
- Environmental NACs may promote fibrotic progression by disrupting BCL2L1 structural stability and altering the lung immune microenvironment.
- BCL2L1-mediated structural toxicity presents a potential biomarker and therapeutic target for pollution-related pulmonary fibrosis.
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