Subacute cadmium exposure modulates Th1 polarization to trigger ER stress-induced porcine hepatocyte apoptosis via regulation of miR-369-TNFα axis.

Abstract

Cadmium (Cd), as a common environmental pollutant, has been reported to cause T lymphocyte dysfunction and cell apoptosis in multiple organs. However, whether subacute Cd exposure can induce apoptosis of hepatocytes and the relationship with Th1/Th2 imbalance were still unclear. In this study, ten 6-week-old piglets were selected and randomly assigned into two groups, the control group and the Cd group. The control group was fed with the standard diet, and for the Cd group, the standard diet was supplemented with 20mg/kg CdCl2; liver tissue was collected on the 40th day of the experiment. Immunofluorescence, qRT-PCR, and western blot were performed to detect the expression of miR-369, Th1/Th2 biomarkers, endoplasmic reticulum (ER) stress-related genes, and apoptotic genes. TUNEL assay was applied to stain apoptotic hepatocytes. In the Cd group, the apoptosis of hepatocytes was significantly increased, and associated with the declined expression of miR-369, Th1 polarization, the elevated expression of ER stress pathway genes and their downstream pro-apoptosis genes, and downregulated expression of anti-apoptotic genes. These results manifest that subacute Cd exposure mediates Th1 polarization to promote ER stress-induced porcine hepatocyte apoptosis via regulating miR-369-TNFα. These results not only provide a basis for the enrichment of Cd toxicology but also support a theoretical foundation for the prevention and therapy of Cd poisoning. Schematic diagram illustrating the proposed mechanism of subacute cadmium exposure modulates Th1 polarization to trigger ER stress-induced porcine hepatocyte apoptosis via regulation of miR-369-TNFα axis.