Role of Glycolysis/Gluconeogenesis and HIF-1 Signaling Pathways in Rats with Dental Fluorosis Integrated Proteomics and Metabolomics Analysis.
Role of Glycolysis/Gluconeogenesis and HIF-1 Signaling Pathways in Rats with Dental Fluorosis Integrated Proteomics and Metabolomics Analysis.
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DOI：
10.3390/ijms23158266
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发表时间：
2022-07-27
影响因子：
5.6
通讯作者：
Yu, Fangfang
中科院分区：
文献类型：
--
作者：
Ba, Yue;Yang, Shuo;Yu, Shuiyuan;Hou, Xiangbo;Du, Yuhui;Gao, Minghui;Zuo, Juan;Sun, Lei;Fu, Xiaoli;Li, Zhiyuan;Huang, Hui;Zhou, Guoyu;Yu, Fangfang
氟化物分布广泛，过量摄入会导致氟斑牙。本研究将6只给予100 mg/L氟化钠的子代大鼠定义为氟斑牙组，8只给予纯净水的子代大鼠定义为对照组。采用液相色谱串联质谱法和气相色谱质谱法对外周血中提取的差异表达蛋白和代谢物进行鉴定，判断标准为倍变>1.2或<0.83,p < 0.05。利用OmicsBean对鉴定的蛋白和代谢物进行共表达富集分析，错误发现率(FDR) < 0.05被认为是显著的。利用人蛋白图谱确定枢纽蛋白的亚细胞分布。基因卡用于验证结果。共鉴定出123个上调蛋白和46个下调蛋白，12个上调代谢物和2个下调代谢物。显著共表达途径为HIF-1 （FDR = 1.86 × 10−3）和糖酵解/糖异生（FDR = 1.14 × 10−10）。验证分析结果表明，与氟相关的蛋白质主要富集在细胞质和质膜细胞质侧的外源成分中。HIF-1通路（FDR = 1.01 × 10−7）也被确定。因此，HIF-1和糖酵解/糖异生途径与氟牙症显著相关。
Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10−3) and glycolysis/gluconeogenesis (FDR = 1.14 × 10−10). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10−7) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.
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