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基于生物信息学方法分析氟化物对成釉细胞毒性作用的分子机制

Molecular mechanism of fluoride toxicity to ameloblasts based on bioinformatics method
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摘要 目的探讨氟化物对成釉细胞毒性作用的分子机制。方法取小鼠成釉细胞株(LS8细胞),根据氟化钠(NaF)终浓度分为对照组(0.0 mmol/L NaF)和染氟组(1.6 mmol/L NaF)。对两组细胞进行转录组测序,筛选差异表达基因(DEGs),对DEGs进行基因本体(GO)分析及基因集富集分析(GSEA)。采用STRING数据库构建DEGs的蛋白-蛋白相互作用(PPI)网络,使用Cytoscape 3.8.0软件对PPI网络进行可视化,筛选关键模块和关键基因。同时,使用实时荧光定量PCR检测关键基因mRNA表达水平,并通过基因表达数据库(GEO数据库)对关键基因进行验证。结果染氟组与对照组比较,共有709个DEGs,其中上调基因223个,下调基因486个。DEGs的GO分析主要涉及受体配体活性、细胞黏附分子结合、细胞外基质结构成分等分子功能,细胞外基质胶原蛋白、受体复合物、膜筏等细胞组分,外部封装结构组织、细胞外结构组织、细胞外基质组织等生物学过程。全基因集的GSEA发现,白细胞介素-17(IL-17)信号通路、真核生物中的核糖体生物发生、核因子κB(NF-κB)信号通路处于激活状态,脂肪酸降解、丙酮酸代谢、脂肪酸代谢处于抑制状态。构建PPI网络后,得到3个关键模块和4个关键基因[Ⅰ型胶原α1(Col1a1)、Ⅰ型胶原α2(Col1a2)、Ⅴ型胶原α1(Col5a1)和纤维蛋白原-1(Fbn1)]。与对照组比较,染氟组LS8细胞Col1a1、Col1a2、Col5a1、Fbn1 mRNA表达水平均较低(P均<0.05),与GEO数据库中基因表达变化趋势一致。结论利用生物信息学方法筛选得到的关键基因Col1a1、Col1a2、Col5a1、Fbn1及IL-17、NF-κB信号通路可能与氟化物对成釉细胞的毒性作用密切相关。 Objective To explore the molecular mechanism of fluoride toxicity to ameloblasts.Methods Mouse ameloblast cell line(LS8 cells)was taken and divided into control group[0.0 mmol/L sodium fluoride(NaF)]and fluoride exposed group(1.6 mmol/L NaF)according to the final concentration of NaF.Transcriptome sequencing was performed to screen differentially expressed genes(DEGs),and gene ontology(GO)analysis and gene set enrichment analysis(GSEA)were performed on DEGs.The STRING database was used to construct the protein-protein interaction(PPI)network of DEGs,and Cytoscape 3.8.0 software was used to visualize the PPI network to screen key modules and key genes.At the same time,real-time fluorescence quantitative PCR was used to detect the mRNA expression level of key genes,and the key genes were verified by gene expression database(GEO database).Results Compared with the control group,there were 709 DEGs in the fluoride exposed group,including 223 up-regulated genes and 486 down-regulated genes.The GO analysis of DEGs mainly involved molecular functions such as receptor-ligand activity,cell adhesion molecule binding,structural components of extracellular matrix,cellular components such as collagen of extracellular matrix,receptor complex,membrane raft,biological processes such as external packaging structure organization,extracellular structure organization,and extracellular matrix organization.The GSEA of the whole gene set found that the interleukin-17(IL-17)signaling pathway,ribosome biogenesis in eukaryotes,and the nuclear factor kappa-B(NF-κB)signaling pathway were activated,while fatty acid degradation,pyruvate metabolism and fatty acid metabolism were inhibited.After constructing PPI network,three key modules and four key genes[typeⅠcollagenα1(Col1a1),typeⅠcollagenα2(Col1a2),typeⅤcollagenα1(Col5a1)and fibrinogen 1(Fbn1)]were obtained.Compared with the control group,the mRNA expression levels of Col1a1,Col1a2,Col5a1 and Fbn1 in LS8 cells of the fluoride exposed group were significantly decreased(P<0.05),which was consistent with the change trend of gene expression in the GEO database.Conclusion Key genes such as Col1a1,Col1a2,Col5a1,Fbn1,and signaling pathways such as IL-17 and NF-κB,which are screened by bioinformatics method,may be closely related to the toxic effects of fluoride on ameloblasts.
作者 刘厚美 白国辉 陈彬 李运航 刘霞 黄婷 田源 Liu Houmei;Bai Guohui;Chen Bin;Li Yunhang;Liu Xia;Huang Ting;Tian Yuan(School of Stomatology,Zunyi Medical University,Zunyi 563000,China;Special Key Laboratory of Oral Disease Research,Higher Education Institution in Guizhou Province,Zunyi 563000,China;The First Clinical College,Zunyi Medical University,Zunyi 563000,China)
出处 《中华地方病学杂志》 CAS 北大核心 2022年第8期619-625,共7页 Chinese Journal of Endemiology
基金 国家自然科学基金(81960198) 贵州省研究生科研基金(黔教合YJSCXJH[2020]168) 贵州省暨遵义市医用生物材料研发人才基地建设项目(黔人领发[2018]3号、遵委[2019]69号)。
关键词 成釉细胞 差异表达基因 生物信息学 Fluorine Ameloblasts Differentially expressed genes Bioinformatics
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