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系统性红斑狼疮和骨质疏松症之间的共享分子特征。

Shared molecular signatures between systemic lupus erythematosus and osteoporosis.

机构信息

Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Environ Toxicol. 2024 Oct;39(10):4744-4753. doi: 10.1002/tox.24313. Epub 2024 Aug 20.

Abstract

This study explores the molecular interplay between systemic lupus erythematosus (SLE) and osteoporosis (OP), aiming to uncover shared gene signatures and pathways for better treatment approaches. Leveraging microarray data from the Gene Expression Omnibus (GEO) database, we employed weighted gene coexpression network analysis to identify coexpression modules in SLE and OP, with subsequent protein-protein interaction analysis clarifying the connections among shared genes. Key genes were pinpointed using CytoHubba and random forest algorithms, validated across independent GEO datasets, and further analyzed through gene set enrichment analysis (GSEA) and immune infiltration studies. We discovered two highly correlated modules in SLE and OP, isolating 30 shared genes and identifying GBP1, SOCS1, IFI16, and XAF1 as central to both conditions. Notably, XAF1 and GBP1 mRNA levels were significantly elevated in the peripheral blood of SLE patients compared with healthy and RA counterparts, underscoring their potential as biomarkers. GSEA and immune infiltration analyses indicated pronounced immune and inflammatory responses, especially in interferon signaling pathways, implicating these core-shared gene networks in the diseases' pathogenesis. The findings highlight the involvement of GBP1, SOCS1, IFI16, and XAF1 in SLE with concurrent OP and suggest that targeting immune and inflammatory responses, particularly through interferon pathways, may offer therapeutic promise for these intertwined conditions.

摘要

本研究旨在探讨系统性红斑狼疮 (SLE) 和骨质疏松症 (OP) 之间的分子相互作用,以发现共同的基因特征和通路,从而为更好的治疗方法提供依据。本研究利用基因表达综合数据库 (GEO) 中的微阵列数据,采用加权基因共表达网络分析 (WGCNA) 鉴定 SLE 和 OP 中的共表达模块,随后通过蛋白质-蛋白质相互作用分析阐明共享基因之间的联系。使用 CytoHubba 和随机森林算法来确定关键基因,通过独立的 GEO 数据集进行验证,并进一步通过基因集富集分析 (GSEA) 和免疫浸润研究进行分析。我们在 SLE 和 OP 中发现了两个高度相关的模块,分离出 30 个共享基因,并确定 GBP1、SOCS1、IFI16 和 XAF1 是这两种疾病的核心基因。值得注意的是,与健康对照组和类风湿关节炎对照组相比,SLE 患者外周血中的 XAF1 和 GBP1 mRNA 水平显著升高,这表明它们可能作为生物标志物。GSEA 和免疫浸润分析表明存在明显的免疫和炎症反应,特别是干扰素信号通路,这表明这些核心共享基因网络参与了疾病的发病机制。这些发现强调了 GBP1、SOCS1、IFI16 和 XAF1 在 SLE 合并 OP 中的作用,并表明针对免疫和炎症反应,特别是通过干扰素通路,可能为这些相互关联的疾病提供治疗前景。

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