Pig lung fibrosis is active in the subacute CdCl2 exposure model and exerts cumulative toxicity through the M1/M2 imbalance

• Published in: Ecotoxicology and environmental safety Vol. 225; p. 112757
• Main Authors: Xu, Shi, Xiaojing, Li, Xinyue, Sun, Wei, Cui, Honggui, Liu, Shiwen, Xu
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2021; Elsevier
• Subjects: CdCl2; Lung fibrosis; M1/M2 imbalance; NF-κB/NLRP3; Pig; HPGD; M1/M2 imbalance; Lung fibrosis; CTGF; NF-κB/NLRP3; NF-κB; α-SMA; GSK-3β; Wnt3a; NLRP3; TIMP1; IL; NOS2; MMP2; FN1; MMP9; Cd Cadmium; PPARγ; Pig; ACTA2; Col1; SP-D; Col3; FPR2 Formyl peptide receptor 2; TNF-α; CdCl2; SP-A; TGFβ; PGR; VIM
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.112757

Environmental pollutant cadmium (Cd) can cause macrophage dysfunction, and the imbalance of M1/M2 is involved in the process of tissue fibrosis. In order to explore the effect of subacute CdCl2 exposure on pig lung tissue fibers and its mechanism, based on the establishment of this model, ICP-MS, H&E staining, Masson staining, Immunofluorescence, RT-PCR, and Western Blot methods were used to detect related indicators. The results found that lung tissue fibrosis, Cd content significantly increased, lung tissue ion disturbance, miR-20a-3p down-regulation, M1/M2 imbalance, LXA4/FPR2 content decreased, MDA content increased, NF-κB/NLRP3, TGFβ pathway, PPARγ/Wnt pathway activated, and the expression of fibrosis-related factors increased. The above results indicate that subacute CdCl2 exposure increase Cd content in the pig lungs, which leads to M1/M2 imbalance and down-regulates the content of LXA4/FPR2, further activates the oxidative stress/NF-κB/NLRP3 pathway, thereby activating the TGFβ and PPARγ/Wnt pathways to induce fibrosis. This study aims to reveal the toxic effects of CdCl2 and will provide new insights into the toxicology of Cd. [Display omitted] •Subacute CdCl2 exposure increases the Cd content in pig lungs and causes mineral metabolism disorders and fibrosis.•CdCl2 exposure induces M1/M2 imbalance by down-regulating miR-20a-3p.•Decreasing the content of LXA4 activates the oxidative stress/NF-κB/NLRP3 pathway and promotes fibrosis process.