Vanadium exposure promotes pulmonary fibrosis via crosstalk between cGAS-STING/NF-κB and Wnt signaling in ducks

Although trace vanadium occurs naturally in animal diets, environmental contamination cumulatively increases dietary exposure and bioaccumulation risks. The lung is highly susceptible to vanadium toxicity, and repeated exposure can promote pulmonary inflammation and fibrotic remodeling. The mechanisms underlying vanadium-induced pulmonary fibrosis remain incompletely understood, particularly the role of cGAS-STING signaling and its interaction with the Wnt pathway. We established a vanadium exposure model in ducks and used network toxicology to assess pulmonary toxicity. KEGG and GO analyses showed enrichment in oxidative stress, NF-κB signaling, Wnt signaling, and processes related to mitochondrial and Golgi apparatus dysfunction. Vanadium exposure resulted in alveolar disruption, collagen accumulation, upregulation of fibrosis markers, mitochondrial and Golgi impairment, and persistent oxidative stress. Molecular analyses revealed time-dependent activation of the cGAS-STING, NF-κB, and Wnt pathways, accompanied by enhanced spatial associations among NF-κB, STING, and Wnt-3a. This study provides initial evidence that dietary vanadium exposure is associated with pulmonary fibrosis in ducks, accompanied by coordinated activation of the cGAS-STING/NF-κB axis and canonical Wnt signaling, and supports a potential inflammatory-to-fibrogenic signaling circuit.