Identifying the potential therapeutic targets of tertiary lymphoid structure in IgA nephropathy based on bioinformatics.

IF 3.1 4区 医学 Q3 IMMUNOLOGY
Autoimmunity Pub Date : 2025-12-01 Epub Date: 2025-06-23 DOI:10.1080/08916934.2025.2519285
Mengxiao Zou, Dan Yang, Han Xu, Shuwang Ge
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引用次数: 0

Abstract

Studies have found that there is tertiary lymphoid structure (TLS) in IgA nephropathy (IgAN), and the existence of TLS has an impact on renal function, creatinine, and proteinuria in patients. We aim to explore the potential molecular mechanisms and therapeutic targets of TLS in IgA nephropathy by bioinformatics methods, hoping to provide treatment methods. The datasets GSE226840, GSE237120, and GSE116626 from the Gene Expression Omnibus (GEO) database were employed to investigate the potential therapeutic targets of TLS in IgAN. The R was used to obtain the differentially expressed genes (DEGs) of three datasets, and the Venny was used to intersect the above three parts of the DEGs to obtain the common DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on obtained genes using Metascape. Protein-Protein interaction (PPI) network was constructed. The intersection of the above common differential genes and IgAN differential genes was obtained by Venny tool. The Nephroseq platform was used to screen core genes and explore their relationship with clinical features. Meanwhile, CIBERSORT was utilized to further delve into the correlation between core genes and immune cells. 92 TLS-related genes and 486 IgAN related genes were obtained, and 6 common genes were obtained after crossing the two genes. The intersection genes were verified by Nephroseq, and CDKN1A, CD83, DUSP6, and CD48 were identified as core genes. At the same time, there were differences in the composition of immune cells between the disease group and the control group when the immune infiltration analysis was performed. And by further analyzing the correlation between core genes and immune cells, the study found that the four genes were positively correlated with T cells, B cells, plasma cells, and other immune cells. By exploring the relationship between core genes and clinical features, CDKN1A and DUSP6 were negatively correlated with Glomerular Filtration Rate (GFR) and positively correlated with proteinuria in IgAN patients. CD48 was negatively correlated with GFR and positively correlated with Blood Urea Nitrogen (BUN). The four genes highly associated with TLS and IgAN were screened using GEO database in study. And CDKN1A, CD83, DUSP6 and CD48 may provide potential therapeutic targets for the treatment of TLS in IgAN. At the same time, studies have found that T cells, B cells, and macrophages may be involved in the formation of TLS in IgAN.

基于生物信息学的IgA肾病三级淋巴结构的潜在治疗靶点识别。
研究发现,IgA肾病(IgAN)中存在三级淋巴结构(TLS), TLS的存在对患者的肾功能、肌酐、蛋白尿有影响。我们旨在通过生物信息学方法探索TLS在IgA肾病中的潜在分子机制和治疗靶点,以期提供治疗方法。利用基因表达综合(GEO)数据库中的GSE226840、GSE237120和GSE116626数据集研究TLS在IgAN中的潜在治疗靶点。用R得到三个数据集的差异表达基因(differential expression genes, deg),用Venny将上述三个部分的deg相交得到共同的deg。利用metscape对获得的基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析。构建蛋白-蛋白相互作用(PPI)网络。通过Venny工具获得上述常见差异基因与IgAN差异基因的交集。使用Nephroseq平台筛选核心基因并探索其与临床特征的关系。同时利用CIBERSORT进一步研究核心基因与免疫细胞的相关性。得到tls相关基因92个,IgAN相关基因486个,两个基因杂交后得到6个共有基因。通过Nephroseq对交叉基因进行验证,鉴定出CDKN1A、CD83、DUSP6和CD48为核心基因。同时,进行免疫浸润分析时,疾病组与对照组的免疫细胞组成也存在差异。通过进一步分析核心基因与免疫细胞的相关性,研究发现这四种基因与T细胞、B细胞、浆细胞等免疫细胞呈正相关。通过探索核心基因与临床特征的关系,CDKN1A和DUSP6与IgAN患者肾小球滤过率(Glomerular Filtration Rate, GFR)呈负相关,与蛋白尿呈正相关。CD48与GFR呈负相关,与血尿素氮(BUN)呈正相关。利用GEO数据库筛选与TLS和IgAN高度相关的4个基因。CDKN1A、CD83、DUSP6和CD48可能为治疗IgAN中的TLS提供潜在的治疗靶点。同时,研究发现,T细胞、B细胞和巨噬细胞可能参与了IgAN中TLS的形成。
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来源期刊
Autoimmunity
Autoimmunity 医学-免疫学
CiteScore
5.70
自引率
8.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.
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