通过生物信息学分析和实验验证鉴定牙周炎中的铁蛋白沉积相关基因

IF 2 3区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Stomatology Oral and Maxillofacial Surgery Pub Date : 2025-09-01 Epub Date: 2025-02-13 DOI:10.1016/j.jormas.2025.102291

Kecong Zhou, Huiwen Chen, Jiachen Dong, Zhongchen Song, Mengjun Sun

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引用次数: 0

摘要

背景：牙周炎是一种多因素的牙周组织慢性炎症性疾病。铁死亡是一种受调控的细胞死亡形式，其特征是铁依赖性脂质过氧化，并参与各种炎症性疾病。本研究旨在鉴定与牙周炎相关的嗜铁相关基因，并通过体外实验进一步验证其相关性。方法：采用普鲁士蓝染色法检测铁的积累和定位。从GSE16134和GSE10334中鉴定出牙周炎差异表达基因，并与上睑下垂基因交叉得到差异表达的上睑下垂基因（FerDEGs）。FerDEGs的功能富集分析采用GO和KEGG进行。通过PPI网络分析筛选枢纽基因。qRT-PCR和Western Blot检测这些枢纽基因在牙龈组织和脂多糖（LPS）刺激下含/不含他铁素-1 （fero -1）的人牙龈成纤维细胞（HGFs）中的表达。结果：牙周炎患者牙龈组织出现上铁质下垂。共鉴定出24个与牙周炎有关的ferdeg。GO分析和KEGG分析显示，内在凋亡信号通路和铁下垂是最富集的通路。PPI网络分析鉴定出5个枢纽基因。脂多糖刺激的炎症牙龈组织和HGFs中，hub基因mRNA表达量显著升高（P < 0.05）。PTGS2和IL6在hgf中的上调表达被fe -1逆转（P < 0.05）。结论：本研究强调了五个与铁中毒相关的基因是未来研究牙周炎发病机制的潜在靶点。

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Identification of ferroptosis-related genes in periodontitis through bioinformatics analysis and experimental validation

Background

Periodontitis is a multifactorial chronic inflammatory disease of periodontal tissues. Ferroptosis is a form of regulated cell death, which is characterized by iron-dependent lipid peroxidation and involved in various inflammatory diseases. This study aims to identify ferroptosis-related genes associated with periodontitis and further validate their relevance through in vitro experiments.

Methods

Iron accumulation and localization were detected using Prussian blue staining. Differentially expressed genes in periodontitis were identified from GSE16134 and GSE10334, and intersected with ferroptosis genes to obtain differentially expressed ferroptosis genes (FerDEGs). Functional enrichment analyses of FerDEGs were performed by GO and KEGG. Hub genes were screened through PPI network analysis. The expression of these hub genes in gingival tissues and in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) with/without ferrostatin-1 (Fer-1) detected by qRT-PCR and Western Blot.

Results

Ferroptosis was observed in gingival tissues affected by periodontitis. A total of 24 FerDEGs involved in periodontitis were identified. GO analysis and KEGG analysis highlighted the intrinsic apoptotic signaling pathway and ferroptosis as the top enriched pathways. PPI network analysis identified five hub genes. The mRNA expression levels of hub genes were significantly higher in inflammatory gingival tissues and HGFs stimulated with LPS (P < 0.05). The upregulated expression of PTGS2 and IL6 in HGFs were reversed by Fer-1 (P < 0.05).