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Abstract：
OBJECTIVE: To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism.
METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively.
RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2\'s relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3.
CONCLUSIONS: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.
METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively.
RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2\'s relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3.
CONCLUSIONS: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.
摘要：
目的：探讨BTG2在牙周炎和糖尿病肾病（DKD）中的作用及其潜在机制。
方法:从基因表达综合(GEO)数据库获得牙周炎和DKD的基因表达数据。差异表达分析鉴定了这些条件之间的共表达基因。NephroseqV5在线肾病数据库验证了这些基因在DKD中的作用。Pearson相关性分析确定了与我们的靶基因相关的基因。我们采用基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）网络来阐明潜在的机制。使用定量聚合酶链反应(qPCR)和免疫荧光测定检查BTG2mRNA的表达水平。蛋白质印迹定量蛋白质参与上皮间质转化（EMT），凋亡，mTORC1信令，和自噬。此外,伤口愈合和流式细胞仪凋亡测定评估足细胞迁移和凋亡，分别。
结果：对GEO数据库数据的分析显示，BTG2是DKD和牙周炎中常见的差异表达基因。与正常情况相比，DKD中的BTG2表达降低，并与蛋白尿相关。GSEA表明BTG2在EMT和mTORC1信号通路中富集。PPI网络强调了BTG2与S100A9、S100A12和FPR1的相关性。免疫荧光测定显示在高葡萄糖(HG)条件下足细胞中BTG2表达显著降低。HG处理的足细胞中BTG2表达降低导致EMT标志物水平升高(α-SMA，波形蛋白）和凋亡蛋白Bim，伴随着nephrin的减少。较低的BTG2水平与足细胞活动和凋亡增加有关，以及升高的RPS6KB1和mTOR水平，但减少自噬标记LC3。
结论：我们的发现表明BTG2是连接DKD和牙周炎的关键中介基因。通过抑制mTORC1信号通路调节自噬,从而抑制EMT，可能在牙周炎和DKD之间的相互作用中起关键作用。
方法:从基因表达综合(GEO)数据库获得牙周炎和DKD的基因表达数据。差异表达分析鉴定了这些条件之间的共表达基因。NephroseqV5在线肾病数据库验证了这些基因在DKD中的作用。Pearson相关性分析确定了与我们的靶基因相关的基因。我们采用基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）网络来阐明潜在的机制。使用定量聚合酶链反应(qPCR)和免疫荧光测定检查BTG2mRNA的表达水平。蛋白质印迹定量蛋白质参与上皮间质转化（EMT），凋亡，mTORC1信令，和自噬。此外,伤口愈合和流式细胞仪凋亡测定评估足细胞迁移和凋亡，分别。
结果：对GEO数据库数据的分析显示，BTG2是DKD和牙周炎中常见的差异表达基因。与正常情况相比，DKD中的BTG2表达降低，并与蛋白尿相关。GSEA表明BTG2在EMT和mTORC1信号通路中富集。PPI网络强调了BTG2与S100A9、S100A12和FPR1的相关性。免疫荧光测定显示在高葡萄糖(HG)条件下足细胞中BTG2表达显著降低。HG处理的足细胞中BTG2表达降低导致EMT标志物水平升高(α-SMA，波形蛋白）和凋亡蛋白Bim，伴随着nephrin的减少。较低的BTG2水平与足细胞活动和凋亡增加有关，以及升高的RPS6KB1和mTOR水平，但减少自噬标记LC3。
结论：我们的发现表明BTG2是连接DKD和牙周炎的关键中介基因。通过抑制mTORC1信号通路调节自噬,从而抑制EMT，可能在牙周炎和DKD之间的相互作用中起关键作用。
