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Sodium Fluoride and Sulfur Dioxide Derivatives Induce TGF-β1-Mediated NBCe1 Downregulation Causing Acid–Base Disorder of LS8 Cells

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Abstract

The aim of the present work was to assess whether the combination of sodium fluoride (NaF) and sulfur dioxide derivatives (SO2 derivatives) affects the expression of the electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4), triggering an acid–base imbalance during enamel development, leading to enamel damage. LS8 cells was taken as the research objects and fluorescent probes, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and factorial analysis were used to clarify the nature of the fluoro-sulfur interaction and the potential signaling pathway involved in the regulation of NBCe1. The results showed that exposure to fluoride or SO2 derivatives resulted in an acid–base imbalance, and these changes were accompanied by inhibited expression of NBCe1 and TGF-β1; these effects were more significant after fluoride exposure as compared to exposure to SO2 derivatives. Interestingly, in most cases, the toxic effects during combined exposure were significantly reduced compared to the effects observed with fluoride or sulfur dioxide derivatives alone. The results also indicated that activation of TGF-β1 signaling significantly upregulated the expression of NBCe1, and this effect was suppressed after the Smad, ERK, and JNK signals were blocked. Furthermore, fluoride and SO2 derivative-dependent NBCe1 regulation was found to require TGF-β1. In conclusion, this study indicates that the combined effect of fluorine and sulfur on LS8 cells is mainly antagonistic. TGF-β1 may regulate NBCe1 and may participate in the occurrence of dental fluorosis through the classic TGF-β1/Smad pathway and the unconventional ERK and JNK pathways.

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Data Availability

“The datasets generated during and/or analyzed during the current study are not publicly available due to (reason(s) why data are not public) but are available from the corresponding author on reasonable request..”

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Funding

This study was supported by the National Natural Science Foundation of China (grant no. 41967051).

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Authors and Affiliations

  1. School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guizhou, China

    Ying Lv, Wentai Wang, Lili Yao, Jiaojiao He, Changhu Lin & Chenglong Tu

  2. Key Laboratory of Oral Disease Research, School of Stomatology, Zunyi Medical University, Zunyi, China

    Guohui Bai

  3. The Toxicity Testing Center of Guizhou Medical University, Guizhou Medical University, Guizhou, China

    Chenglong Tu

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  1. Ying Lv
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Lv, Y., Wang, W., Yao, L. et al. Sodium Fluoride and Sulfur Dioxide Derivatives Induce TGF-β1-Mediated NBCe1 Downregulation Causing Acid–Base Disorder of LS8 Cells. Biol Trace Elem Res 201, 828–842 (2023). https://doi.org/10.1007/s12011-022-03169-8

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