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引用次数: 0
摘要
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,旨在发现共同的基因特征和通路,从而找到更好的治疗方法。利用基因表达总库(GEO)数据库中的微阵列数据,我们采用加权基因共表达网络分析来确定系统性红斑狼疮和骨质疏松症的共表达模块,并通过随后的蛋白-蛋白相互作用分析来阐明共享基因之间的联系。我们使用 CytoHubba 和随机森林算法精确定位了关键基因,并在独立的 GEO 数据集中进行了验证,还通过基因组富集分析(GSEA)和免疫浸润研究进行了进一步分析。我们在 SLE 和 OP 中发现了两个高度相关的模块,分离出了 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,在系统性红斑狼疮患者的外周血中,XAF1 和 GBP1 的 mRNA 水平与健康人和 RA 患者相比明显升高,这凸显了它们作为生物标记物的潜力。GSEA和免疫浸润分析表明了明显的免疫和炎症反应,尤其是在干扰素信号通路中,这表明这些核心共享基因网络与疾病的发病机制有关。研究结果表明,GBP1、SOCS1、IFI16 和 XAF1 参与了并发 OP 的系统性红斑狼疮的发病,并表明针对免疫和炎症反应,尤其是通过干扰素通路,可能会为这些相互交织的疾病提供治疗前景。
Shared molecular signatures between systemic lupus erythematosus and osteoporosis
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.
期刊介绍:
The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are:
Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration;
Natural toxins and their impacts;
Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation;
Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard;
Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.