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Shared molecular signatures between systemic lupus erythematosus and osteoporosis.
Environmental Toxicology ( IF 4.4 ) Pub Date : 2024-08-20 , DOI: 10.1002/tox.24313
Xin Yuan 1 , Ze-Mao Zheng 2 , Weinan Lai 1
Affiliation  

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.

中文翻译:


系统性红斑狼疮和骨质疏松症之间的共同分子特征。



本研究探讨了系统性红斑狼疮 (SLE) 和骨质疏松症 (OP) 之间的分子相互作用,旨在揭示共同的基因特征和通路,以获得更好的治疗方法。利用来自基因表达综合 (GEO) 数据库的微阵列数据,我们采用加权基因共表达网络分析来识别 SLE 和 OP 中的共表达模块,随后的蛋白质-蛋白质相互作用分析阐明了共享基因之间的联系。使用 CytoHubba 和随机森林算法精确定位关键基因,在独立的 GEO 数据集中验证,并通过基因集富集分析 (GSEA) 和免疫浸润研究进一步分析。我们在 SLE 和 OP 中发现了两个高度相关的模块,分离了 30 个共享基因,并将 GBP1 、 SOCS1 、 IFI16 和 XAF1 确定为这两种情况的中心。值得注意的是,与健康患者和 RA 患者相比,SLE 患者外周血中的 XAF1 和 GBP1 mRNA 水平显著升高,突显了它们作为生物标志物的潜力。GSEA 和免疫浸润分析表明明显的免疫和炎症反应,尤其是在干扰素信号通路中,表明这些核心共享基因网络与疾病的发病机制有关。研究结果强调了 GBP1、SOCS1、IFI16 和 XAF1 与 SLE 并发 OP 的关系,并表明靶向免疫和炎症反应,特别是通过干扰素途径,可能为这些交织在一起的疾病提供治疗前景。
更新日期:2024-08-20
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