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Proteomics Sequencing Reveals the Role of TGF-β Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride

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Abstract

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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Data Availability

During the present study, all the generated datasets and analyzed data are available from the corresponding author upon reasonable request.

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Funding

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).

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Authors and Affiliations

  1. Department of Environmental Health, School of Public Health, Environment and Health Innovation Team, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China

    Fang-fang Yu, Shui-yuan Yu, Shuo Yang, Xiang-bo Hou, Yu-hui Du, Ming-hui Gao, Juan Zuo, Lei Sun, Xiao-li Fu, Zhi-yuan Li, Hui Huang, Guo-yu Zhou & Yue Ba

  2. Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China

    Lei-zhen Duan

  3. Outpatient Department, Zhengyang County People’s Hospital, Zhumadian, Henan, China

    Dao-li Jia

  4. Jinshui District Center for Disease Control and Prevention, Zhengzhou, Henan, China

    Rui-qin Chen

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  1. Fang-fang Yu
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Contributions

Fang-fang Yu: methodology, writing, review and editing, and funding acquisition. Shui-yuan Yu, Lei-zhen Duan, and Shuo Yang: data curation, visualization, and writing, original draft. Xiang-bo Hou, Yu-hui Du, Ming-hui Gao, Juan Zuo, and Lei Sun: investigation, visualization, and data curation. Xiao-li Fu, Hui Huang, Zhi-yuan Li, Guo-yu Zhou, Dao-li Jia, Rui-qin Chen, and Yue Ba: supervision, resources, and writing, review and editing.

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Correspondence to Yue Ba.

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All animal studies were reviewed and approved by the animal ethics research committee of Zhengzhou University.

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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 202, 2100–2110 (2024). https://doi.org/10.1007/s12011-023-03805-x

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