Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Heilongjiang Academy of Medical Sciences, Harbin, China.
PLoS One. 2022 Jul 28;17(7):e0271202. doi: 10.1371/journal.pone.0271202. eCollection 2022.
Cell survival or death is one of the key scientific issues of inflammatory response. To regulate cell death during the occurrence and development of periodontitis, various forms of programmed cell death, such as pyroptosis, ferroptosis, necroptosis, and apoptosis, have been proposed. It has been found that ferroptosis characterized by iron-dependent lipid peroxidation is involved in cancer, degenerative brain diseases and inflammatory diseases. Furthermore, NCOA4 is considered one of ferroptosis-related genes (FRGs) contributing to butyrate-induced cell death in the periodontitis. This research aims to analyze the expression of FRGs in periodontitis tissues and to explore the relationship between ferroptosis and periodontitis.
Genes associated with periodontitis were retrieved from two Gene Expression Omnibus datasets. Then, we normalized microarray data and removed the batch effect using the R software. We used R to convert the mRNA expression data and collected the expression of FRGs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), transcription factor (TF) and protein-protein interaction (PPI) network analyses were used. In addition, we constructed a receiver operating characteristic curve and obtained relative mRNA expression verified by quantitative reverse-transcription polymerase chain reaction (PCR).
Eight and 10 FRGs related to periodontitis were upregulated and downregulated, respectively. GO analysis showed that FRGs were enriched in the regulation of glutathione biosynthetic, glutamate homeostasis, and endoplasmic reticulum-nucleus signaling pathway. The top TFs included CEBPB, JUND, ATF2. Based on the PPI network analysis, FRGs were mainly linked to the negative regulation of IRE1-mediated unfolded protein response, regulation of type IIa hypersensitivity, and regulation of apoptotic cell clearance. The expression levels of NCOA4, SLC1A5 and HSPB1 using PCR were significantly different between normal gingival samples and periodontitis samples. Furthermore, the diagnostic value of FRGs for periodontitis were "Good".
We found significant associations between FRGs and periodontitis. The present study not only provides a new possible pathomechanism for the occurrence of periodontitis but also offers a new direction for the diagnosis and treatment of periodontitis.
细胞存活或死亡是炎症反应的关键科学问题之一。为了调节牙周炎发生发展过程中的细胞死亡，已经提出了各种形式的程序性细胞死亡，如细胞焦亡、铁死亡、坏死性凋亡和细胞凋亡。已经发现，铁依赖性脂质过氧化作用的铁死亡与癌症、退行性脑部疾病和炎症性疾病有关。此外，NCOA4 被认为是与丁酸盐诱导的牙周炎细胞死亡相关的铁死亡相关基因 (FRGs) 之一。本研究旨在分析 FRGs 在牙周炎组织中的表达，并探讨铁死亡与牙周炎的关系。
从两个基因表达综合数据库中检索与牙周炎相关的基因。然后，我们使用 R 软件对微阵列数据进行标准化并去除批次效应。我们使用 R 转换 mRNA 表达数据，并收集 FRGs 的表达。进行基因本体论 (GO)、京都基因与基因组百科全书 (KEGG)、转录因子 (TF) 和蛋白质-蛋白质相互作用 (PPI) 网络分析。此外，我们构建了接收器工作特性曲线，并通过定量逆转录聚合酶链反应 (PCR) 获得了相对 mRNA 表达的验证。
分别有 8 个和 10 个 FRGs 上调和下调与牙周炎相关。GO 分析表明，FRGs 富集于谷胱甘肽生物合成的调控、谷氨酸稳态和内质网-核信号通路。顶级 TF 包括 CEBPB、JUND、ATF2。基于 PPI 网络分析，FRGs 主要与 IRE1 介导的未折叠蛋白反应的负调控、IIa 型超敏反应的调控以及凋亡细胞清除的调控相关。使用 PCR 检测到 NCOA4、SLC1A5 和 HSPB1 的表达水平在正常牙龈样本和牙周炎样本之间有显著差异。此外，FRGs 对牙周炎的诊断价值为“良好”。
我们发现 FRGs 与牙周炎之间存在显著关联。本研究不仅为牙周炎的发生提供了一个新的可能的发病机制，也为牙周炎的诊断和治疗提供了一个新的方向。
