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.

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