Exploring the crosstalk molecular mechanisms between IgA nephropathy and Sjögren's syndrome based on comprehensive bioinformatics and immunohistochemical analyses.

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Peng He, Lei Wei, Ruijing Zhang, Jin Zhao, Yuzhan Zhang, Liuyifei Huang, Xiao Bai, Xiaoxuan Ning, Shiren Sun
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Abstract

IgA nephropathy (IgAN) and Sjogren's syndrome (SS) are two autoimmune diseases with undetermined etiology and related to abnormal activation of lymphocytes. This study aims to explore the crucial genes, pathways and immune cells between IgAN and SS. Gene expression profiles of IgAN and SS were obtained from the Gene Expression Omnibus and Nephroseq data. Differentially expressed gene (DEG) and weighted gene co-expression network analyses (WGCNA) were done to identify common genes. Enrichment analysis and protein-protein interaction network were used to explore potential molecular pathways and crosstalk genes between IgAN and SS. The results were further verified by external validation and immunohistochemistry (IHC) analysis. Additionally, immune cell analysis and transcription factor prediction were also conducted. The DEG analysis revealed 28 commonly up-regulated genes, while WGCNA identified 98 interactively positive-correlated module genes between IgAN and SS. The enrichment analysis suggested that these genes were mainly involved in the biological processes of response to virus and antigen processing and presentation. The external validation and IHC analysis identified 5 hub genes (PSMB8, PSMB9, IFI44, ISG15, and CD53). In the immune cell analysis, the effector memory CD8 T and T follicular helper cells were significantly activated, and the corresponding proportions showed positively correlations with the expressions of the 5 hub genes in the two autoimmune diseases. Together, our data identified the crosstalk genes, molecular pathways, and immune cells underlying the IgAN and SS, which provides valuable insights into the intricate mechanisms of these diseases and offers potential intervention targets.

Abstract Image

基于全面的生物信息学和免疫组化分析,探索 IgA 肾病和 Sjögren's 综合征之间的串联分子机制。
IgA 肾病(IgAN)和斯约格伦综合征(SS)是两种病因未明的自身免疫性疾病,与淋巴细胞的异常激活有关。本研究旨在探索 IgAN 和 SS 之间的关键基因、通路和免疫细胞。研究人员从基因表达总库(Gene Expression Omnibus)和Nephroseq数据中获得了IgAN和SS的基因表达谱。通过差异表达基因(DEG)和加权基因共表达网络分析(WGCNA)找出共同基因。富集分析和蛋白-蛋白相互作用网络用于探索 IgAN 和 SS 之间潜在的分子通路和串联基因。外部验证和免疫组化(IHC)分析进一步验证了这些结果。此外,还进行了免疫细胞分析和转录因子预测。DEG分析发现了28个常见的上调基因,而WGCNA则发现了98个IgAN和SS之间交互正相关的模块基因。富集分析表明,这些基因主要参与了对病毒的反应和抗原处理及呈递的生物学过程。外部验证和 IHC 分析确定了 5 个枢纽基因(PSMB8、PSMB9、IFI44、ISG15 和 CD53)。在免疫细胞分析中,效应记忆CD8 T细胞和T滤泡辅助细胞被显著激活,相应的比例与这两种自身免疫性疾病中5个中心基因的表达呈正相关。总之,我们的数据确定了IgAN和SS背后的串联基因、分子通路和免疫细胞,为了解这些疾病的复杂机制提供了有价值的见解,并提供了潜在的干预靶点。
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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