利用竞争性内源性 RNA 网络鉴定和验证牙周炎中与老化和内质网压力相关的基因

IF 4.5 2区 医学 Q2 CELL BIOLOGY Inflammation Pub Date : 2024-08-13 DOI:10.1007/s10753-024-02124-0
Xinran Feng, Da Peng, Yunjing Qiu, Qian Guo, Xiaoyu Zhang, Zhixuan Li, Chunling Pan
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引用次数: 0

摘要

牙周炎是一种破坏牙周的多因素慢性炎症性疾病。除了微生物感染和宿主免疫反应外,新的证据显示衰老和内质网应激(ER应激)在牙周炎发病机制中起着关键作用。本研究旨在确定牙周炎中的衰老相关基因(ARGs)和内质网应激相关基因(ERGs)。我们从基因表达总库(Gene Expression Omnibus,GEO)、人类老龄化基因组资源(Human Ageing Genomic Resources,HAGR)和基因卡片(GeneCards)数据库中获取数据,分别鉴定差异表达的mRNAs/miRNAs/lncRNAs(DEmRNAs/DEmiRNAs/DElncRNAs)、ARGs和ERGs。我们利用 MultiMiR 数据库对 miRNA 进行反向预测,并利用 STARBase 数据库预测 miRNA 与 lncRNA 之间的相互作用。之后,我们构建了一个mRNA-miRNA-lncRNA ceRNA网络。随后,我们发现了10个枢纽基因,即LCK、LYN、CXCL8、IL6、HCK、IL1B、BTK、CXCL12、GNAI1和FCER1G,以及5个DEMRNAs-ARGs-ERGs。此外,我们还进行了加权基因共表达网络分析(WGCNA)和单样本基因组富集分析(ssGSEA),以分别探索共表达模块和免疫浸润。最后,我们利用透射电子显微镜(TEM)、倒置荧光显微镜、实时定量聚合酶链反应(qRT-PCR)和Western Blot对感染牙龈卟啉单胞菌(P. gingivalis)的牙周韧带干细胞(PDLSCs)的生物信息学结果进行了验证。实验结果广泛证实了生物信息分析的准确性。本研究建立了牙周炎中与衰老和ER应激相关的ceRNA网络,有助于深入了解牙周炎的发病机制。
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Identification and Validation of Aging- and Endoplasmic Reticulum Stress-Related Genes in Periodontitis Using a Competing Endogenous RNA Network.

Periodontitis is a multifactorial chronic inflammatory disease that destroy periodontium. Apart from microbial infection and host immune responses, emerging evidence shows aging and endoplasmic reticulum stress (ER stress) play a key role in periodontitis pathogenesis. The aim of this study is to identify aging-related genes (ARGs) and endoplasmic reticulum stress-related genes (ERGs) in periodontitis. Data were obtained from the Gene Expression Omnibus (GEO), Human Ageing Genomic Resources (HAGR) and GeneCards databases to identify differentially expressed mRNAs/miRNAs/lncRNAs (DEmRNAs/DEmiRNAs/DElncRNAs), ARGs and ERGs, respectively. We used the MultiMiR database for the reverse prediction of miRNAs and predicted miRNA-lncRNA interactions using the STARBase database. Afterwards, we constructed a mRNA-miRNA-lncRNA ceRNA network. A total of 10 hub genes, namely LCK, LYN, CXCL8, IL6, HCK, IL1B, BTK, CXCL12, GNAI1 and FCER1G, and 5 DEmRNAs-ARGs-ERGs were then discovered. Further, weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) were performed to explore co-expression modules and immune infiltration respectively. Finally, we used transmission electron microscope (TEM), inverted fluorescence microscopy, quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to verify the bioinformatic results in periodontal ligament stem cells (PDLSCs) infected with Porphyromonas gingivalis (P. gingivalis). The experimental results broadly confirmed the accuracy of bioinformatic analysis. The present study established an aging- and ER stress-related ceRNA network in periodontitis, contributing to a deeper understanding of the pathogenesis of periodontitis.

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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