Cadmium Exposure Affects the Expression of miR-130a and miR-532, Causing Th1/Th2 Imbalance and Inducing Apoptosis via Endoplasmic Reticulum Stress Pathway in Pig Lung.

Cadmium (Cd), as a common environmental pollutant, spreads in the ecosystem through nutrient transfer, posing potential hazards to livestock health and indirectly harming humans through the food chain. Cd can impair the immune function. Interestingly, Cd can also cause lung damage through apoptosis, but the mechanism of its lung toxicity remains unclear. MicroRNAs (miRNAs) are key post-transcriptional regulators implicated in various pathological processes, including inflammation and apoptosis. In this experiment, a pig model of Cd poisoning was established by administering 20 mg/kg CdCl₂ to the diet over a 40-day period. The actual Cd accumulation in pig lung tissue was confirmed by ICP-MS. Results showed that Cd exposure downregulated miR-130a and upregulated miR-532 in pig lung tissue. Bioinformatics prediction and experimental verification confirmed that miR-130a directly targets the Th1 marker tumor necrosis factor-α (TNF-α), while miR-532 targets the Th2 marker chemokine receptor 4 (CCR4). Downregulation of miR-130a relieved its inhibitory effect on TNF-α, and upregulation of miR-532 inhibited on CCR4, leading to a shift in the Th1/Th2 balance toward Th1. Furthermore, the Th1/Th2 imbalance induced by Cd activated the endoplasmic reticulum stress (ERS) pathway. The activated ERS pathway subsequently induced apoptosis. Collectively, our findings demonstrate that Cd exposure regulates the miR-130a/TNF-α and miR-532/CCR4 axes to induce Th1/Th2 imbalance, which further triggers ERS-mediated apoptosis in pig lung tissue. These observational results provide a reference solution for the pathogenesis of Cd-induced lung diseases in pigs, and lay a research foundation for the prevention and treatment intervention of Cd-related diseases in the livestock industry.