Deoxynivalenol induces cell senescence in RAW264.7 macrophages via HIF-1α-mediated activation of the p53/p21 pathway

Deoxynivalenol (DON), a potent mycotoxin, exhibits strong immunotoxicity and poses a significant threat to human and animal health. Cell senescence has been implicated in the immunomodulatory effects of DON; however, the potential of DON to induce cell senescence remains inadequately explored. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) serves as a crucial target of mycotoxins and is closely involved in cell senescence. To investigate this potential, we employed the RAW264.7 macrophage model and treated the cells with varying concentrations of DON (2-8 μM) for 24 h. Transcriptome analysis revealed that 2365 genes were significantly upregulation while 2405 genes were significantly decreased after exposure to DON. KEGG pathway enrichment analysis demonstrated substantial enrichment in pathways associated with cellular senescence and hypoxia. Remarkably, we observed a rapid and sustained increase in HIF-1α expression following DON treatment. DON induced cell senescence through the activation of the p53/p21