Luo Rong, Liang Zhenye, Chen Huijun, Bao Dandan, Lin Xinlu
Department of Pharmacy, Taizhou First People's Hospital, Taizhou, China.
PLoS One. 2025 Apr 2;20(4):e0320061. doi: 10.1371/journal.pone.0320061. eCollection 2025.
Diabetes Mellitus type 2 (DM2) is thought to have a bidirectional relationship with Periodontitis (PD). However, the complex molecular interactions between DM2 and PD remain unclear. This study aimed to explore the shared genes and common signatures of DM2 and PD via bioinformatic analysis.
Firstly, using bioinformatic methods to investigate common genes. The series matrix files of GSE6751 for DM and GSE15932 for PD were downloaded from the Gene Expression Omnibus (GEO) database. The data was normalized using the R package, and the limma package was utilized to identify the Differentially Expressed Genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of DEGs were performed using the "clusterProfiler" package in the R software. The protein-protein network was constructed to analyze the potential relationship among the proteins. CytoHubba, a plugin for the Cytoscape software, was used to identify the hub genes. The validation datasets selected for DM2 and PD were GSE10334 and GSE7014, respectively. Receiver Operating Characteristic (ROC) curve analysis was performed to obtain the area under the ROC curve. Lipopolysaccharide (LPS) + high glucose-induced DM-related PD was simulated to verify the three hub genes through quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot (WB).
In total, 44 common DEGs were identified. ITGAM, H2BC21, S100A9 was identified as he hub genes of DM2 and PD, with all of them were up-regulated. In addition, the area under the curve of all three hub genes was more than 0.65. In-vitro experiments revealed that the relative expression of S100A9 was increased after the treatment with LPS + high glucose. Besides, TLR4 and p-NF-κB levels were also improved in model group.
S100A9 was identified as the hub gene of DM2 and PD. S100A9 could trigger TLR4 signaling way to promote disease development, which can be the potential targets for diagnosis and treatment.
2型糖尿病（DM2）与牙周炎（PD）被认为存在双向关系。然而，DM2与PD之间复杂的分子相互作用仍不清楚。本研究旨在通过生物信息学分析探索DM2和PD的共享基因及共同特征。
首先，运用生物信息学方法研究共同基因。从基因表达综合数据库（GEO）下载DM的GSE6751系列矩阵文件和PD的GSE15932系列矩阵文件。使用R包对数据进行标准化处理，并利用limma包识别差异表达基因（DEGs）。使用R软件中的“clusterProfiler”包对DEGs进行基因本体论和京都基因与基因组百科全书富集分析。构建蛋白质-蛋白质网络以分析蛋白质之间的潜在关系。使用Cytoscape软件的插件CytoHubba识别枢纽基因。为DM2和PD选择的验证数据集分别为GSE10334和GSE7014。进行受试者工作特征（ROC）曲线分析以获得ROC曲线下面积。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法（WB）模拟脂多糖（LPS）+高糖诱导的DM相关PD，以验证这三个枢纽基因。
总共鉴定出44个共同的DEGs。ITGAM、H2BC21、S100A9被鉴定为DM2和PD的枢纽基因，它们均上调。此外，所有三个枢纽基因的曲线下面积均大于0.65。体外实验表明，LPS+高糖处理后S100A9的相对表达增加。此外，模型组中TLR4和p-NF-κB水平也有所提高。
S100A9被鉴定为DM2和PD的枢纽基因。S100A9可触发TLR4信号通路促进疾病发展，这可为诊断和治疗提供潜在靶点。
