Mechanistic insights into cobalt-induced lung injury: An integrated network toxicology and bioinformatics approach

Abstract

Background

The widespread environmental contamination by cobalt compounds, coupled with their documented respiratory toxicities, has become a pressing public health concern. Current mechanistic research on the health impacts of these substances lacks coherence and integration, highlighting the need for a comprehensive investigation into the mechanisms of cobalt-induced lung injury.

Methods

Utilizing CTDbase and NetInfer databases, we obtained target genes of cobalt and its compound and ascertained their associated lung adverse outcomes. Disease-related targets were retrieved from OMIM, DisGeNet, GeneCards, and NCBI databases. A protein-protein interaction (PPI) network was constructed to identify the core targets between compounds and diseases. Based on the DAVID database, enrichment pathways were evaluated by GO and KEGG analyses. Finally, single-cell analysis was conducted to investigate specific cell types implicated in the cobalt-induced lung hazards.

Results

Pulmonary hypertension (PH) was determined as the most critical lung injury associated with cobalt compounds. In total, we identified 275 compound-related and 3146 PH-related targets, ultimately pinpointing 169 overlapping targets. Among these, 28 pivotal co-targets were implicated in cobalt and its compound-induced PH, including IL6, AKT1, TNF, TP53, NFKB1, HIF1A, etc., which were primarily involved in the IL-17, TNF, and HIF-1 signaling pathways. Moreover, monocytes and macrophages were recognized as effector cells underlying the induction of PH by cobalt exposure, with CXCL8 and HIF1A serving as signature genes.

Conclusion

Our study not only elucidates pivotal target genes, pathways, and specific cell types involved in cobalt-induced lung hazards, but also establishes a novel approach to clarify the mechanisms underlying metal toxicity.