The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography–tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-β (TGF-β) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-β signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-β signaling pathway, in which RhoA may play a key role.
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During the present study, all the generated datasets and analyzed data are available from the corresponding author upon reasonable request.
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This work was supported by the National Natural Scientific Foundation of China (82003400, 81972981) and the Science and Technology Program of Henan Province (232102311079, 212102310622).
All animal studies were reviewed and approved by the animal ethics research committee of Zhengzhou University.
The authors declare no competing interests.
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Yu, Ff., Yu, Sy., Duan, Lz. et al. Proteomics Sequencing Reveals the Role of TGF-β Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride. Biol Trace Elem Res (2023). https://doi.org/10.1007/s12011-023-03805-x