Inorganic arsenic promotes apoptosis of human immortal keratinocytes through the TGF-β1/ERK signaling pathway

Chronic exposure to high-dose inorganic arsenic through groundwater, air, or food remains a major environmental public health issue worldwide. Apoptosis, a method of cell death, has recently become a hot topic of research in biology and medicine. Previous studies have demonstrated that extracellular signal-regulated kinase (ERK) is related to arsenic-induced Apoptosis. However, the reports are contradictory, and the knowledge of the above-mentioned mechanisms and their mutual regulation remains limited. In this study, the associations between the TGF-β1/ERK signaling pathway and arsenic-induced cell Apoptosis were confirmed using the HaCaT cell model. The relative expressions of the indicators of the TGF-β1/ERK signaling pathway, apoptosis-related genes (cytochrome C, Caspase-3, caspase-9, cleaved Caspase-3, cleaved caspase-9, and Bax), the mitochondrial membrane potential, and the total Apoptosis rate were significantly increased (P < .05), while the expression of the antiapoptosis gene Bcl-2 was significantly decreased (P < .05) in cells of the group exposed to arsenic. Moreover, the results demonstrated that the ERK Inhibitor (PD98059) and TGF-β1 inhibitor (LY364947) could inhibit the activation of the ERK signaling pathway, thereby reducing the mitochondrial membrane potential, the total Apoptosis rate, and the expression of pro-apoptosis-related genes in the cells, while the expression of the antiapoptosis gene Bcl-2 was significantly increased (P < .05). By contrast, the recombinant human TGF-β1 could promote Apoptosis of the HaCaT cells by increasing the activation of the ERK signaling pathway (P < .05). These results indicate that inorganic arsenic promotes the Apoptosis of human immortal keratinocytes through the TGF-β1/ERK signaling pathway.