基于生物信息学分析鉴定氧化应激相关基因（OSRGs）作为治疗牙周炎的潜在靶点。
Identifying Oxidative Stress-Related Genes (OSRGs) as Potential Target for Treating Periodontitis Based on Bioinformatics Analysis.
机构信息
Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, District, Shanghai, 200011, China.
出版信息
Comb Chem High Throughput Screen. 2024;27(8):1191-1204. doi: 10.2174/1386207326666230821102623.
BACKGROUND
Periodontitis (PD) is a multifactorial inflammatory disease that is closely associated with periodontopathic bacteria. Numerous studies have demonstrated oxidative stress (OS) contributes to inflammation and is a prime factor in the development of PD. It is imperative to explore the function of newly discovered hub genes associated with OS in the advancement of PD, thereby identifying potential targets for therapeutic intervention.
OBJECTIVES
The goal of the current study was to identify the oxidative-stress-related genes (OSRGs) associated with periodontitis (PD) development using an integrated bioinformatics method.
METHODS
DEGs from GEO gene-expression data were identified using the "limma" package. We obtained OSRGs from GeneCards and utilized a Venn diagram to uncover differentially expressed OSRGs (DEOSRGs). After receiving the DEOSRGs, we employed Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analytical tools to examine their possible functions and pathways in PD. Receiver operating characteristic (ROC) curves screened for hub genes of PD. RT-qPCR and western blot analysis were used to detect DEOSRG expression in mouse ligature-induced periodontitis gingival tissues.
RESULTS
The investigation identified 273 OSRGs. Based on PPI analysis, we recognized 20 OSRGs as hub genes. GO and KEGG enrichment analysis indicated that these hub genes were predominantly enriched in leukocyte migration, lymphocyte proliferation, and humoral immune response, and associated with leukocyte trans-endothelial migration, cytokine-cytokine receptor interaction, and NF-κB signaling pathway. Following ROC analysis, VCAM1, ITGAM, FCGR3A, IL1A, PECAM1, and VCAM1were identified as PD prognostic gene. RT-qPCR and western blot analyses confirmed that the expression ITGAM, FCGR3A, and PECAM1 were significantly elevated in the gingival tissues obtained from mice.
CONCLUSION
This investigation revealed that ITGAM, FCGR3A, and PECAM1 may have a crucial function in the advancement of PD.
背景
牙周炎（PD）是一种多因素炎症性疾病，与牙周病细菌密切相关。大量研究表明，氧化应激（OS）有助于炎症，是 PD 发展的主要因素。因此，探索与 OS 相关的新发现的 PD 进展相关的枢纽基因的功能，从而确定潜在的治疗干预靶点至关重要。
目的
本研究旨在采用综合生物信息学方法，确定与牙周炎（PD）发展相关的氧化应激相关基因（OSRGs）。
方法
使用“limma”包从 GEO 基因表达数据中鉴定差异表达基因（DEGs）。我们从 GeneCards 中获得 OSRGs，并使用 Venn 图揭示差异表达的 OSRGs（DEOSRGs）。获得 DEOSRGs 后，我们采用基因本体论（GO）、京都基因与基因组百科全书（KEGG）和蛋白质-蛋白质相互作用（PPI）分析工具，研究它们在 PD 中的可能功能和途径。接受者操作特征（ROC）曲线筛选 PD 的枢纽基因。RT-qPCR 和 Western blot 分析用于检测小鼠结扎诱导牙周炎牙龈组织中 DEOSRG 的表达。
结果
研究发现 273 个 OSRGs。基于 PPI 分析，我们识别出 20 个 OSRGs 作为枢纽基因。GO 和 KEGG 富集分析表明，这些枢纽基因主要富集于白细胞迁移、淋巴细胞增殖和体液免疫反应，并与白细胞跨内皮迁移、细胞因子-细胞因子受体相互作用和 NF-κB 信号通路相关。经 ROC 分析，VCAM1、ITGAM、FCGR3A、IL1A、PECAM1 和 VCAM1 被鉴定为 PD 预后基因。RT-qPCR 和 Western blot 分析证实，在从小鼠获得的牙龈组织中，ITGAM、FCGR3A 和 PECAM1 的表达显著升高。
结论
本研究表明，ITGAM、FCGR3A 和 PECAM1 可能在 PD 的进展中具有重要作用。
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