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基于转录组数据揭示狼疮肾炎患者血液、肾小球和小管间质中常见的差异 mRNA、信号通路和免疫细胞。

Revealing common differential mRNAs, signaling pathways, and immune cells in blood, glomeruli, and tubulointerstitium of lupus nephritis patients based on transcriptomic data.

机构信息

Department of Nephrology, Dongying People's Hospital, Dongying, China.

出版信息

Ren Fail. 2023 Dec;45(1):2215344. doi: 10.1080/0886022X.2023.2215344.

Abstract

Lupus nephritis (LN) is a potentially fatal autoimmune disease. The purpose of this study was to find potential key molecular markers of LN to aid in the early diagnosis and management of the disease. Datasets GSE99967_blood, GSE32591_glomeruli, and GSE32591_tubulointerstitium were included in this study. Differentially expressed mRNAs (DEmRNAs) were identified between the normal control and LN groups using the limma package in R. Common DEmRNAs in the three datasets were taken. Subsequently, functional enrichment analysis, immune correlation analysis, receiver operating characteristic (ROC) curve analysis and real-time polymerase chain reaction (RT-PCR) verification were performed. In this study, 11 common DEmRNAs were obtained and all of them were up-regulated. In protein-protein interaction (PPI) networks, we found that MX dynamin like GTPase 1 (MX1) and radical S-adenosyl methionine domain containing 2 (RSAD2) had the highest interaction score (0.997). Functional enrichment analysis revealed that MX1 and RSAD2 were enriched in influenza A and hepatitis C signaling pathways. The area under the curve (AUC) values of interferon-induced protein 44 (IFI44) and MX1 in GSE32591_glomeruli and GSE32591_tubulointerstitium datasets are 1, which is worthy of further study on their diagnostic value and molecular mechanism. The xCell analysis showed abnormal distribution of granulocyte-macrophage progenitor (GMP) cells in blood, glomeruli, and tubulointerstitium. Pearson's correlation analysis found that GMP cells were significantly correlated with lactotransferrin (LTF) and cell cycle. Identification of common DEmRNAs and key pathways in the blood, glomeruli, and tubulointerstitium of patients with LN provides potential research directions for exploring the molecular mechanisms of the disease.

摘要

狼疮性肾炎(LN)是一种潜在致命的自身免疫性疾病。本研究旨在寻找 LN 的潜在关键分子标志物,以辅助疾病的早期诊断和治疗。本研究纳入了数据集 GSE99967_blood、GSE32591_glomeruli 和 GSE32591_tubulointerstitium。使用 R 中的 limma 软件包鉴定正常对照组和 LN 组之间的差异表达信使 RNA(DEmRNAs)。取三个数据集之间的共同 DEmRNAs。随后进行功能富集分析、免疫相关性分析、接受者操作特征(ROC)曲线分析和实时聚合酶链反应(RT-PCR)验证。本研究获得了 11 个共同的 DEmRNAs,它们均上调。在蛋白质-蛋白质相互作用(PPI)网络中,我们发现 MX 动力蛋白样 GTP 酶 1(MX1)和激进 S-腺苷甲硫氨酸结构域包含 2(RSAD2)具有最高的相互作用评分(0.997)。功能富集分析表明,MX1 和 RSAD2 富集在流感 A 和丙型肝炎信号通路中。干扰素诱导蛋白 44(IFI44)和 MX1 在 GSE32591_glomeruli 和 GSE32591_tubulointerstitium 数据集的曲线下面积(AUC)值为 1,这值得进一步研究其诊断价值和分子机制。xCell 分析表明,粒细胞-巨噬细胞祖细胞(GMP)在血液、肾小球和肾小管间质中的分布异常。Pearson 相关性分析发现 GMP 细胞与乳铁蛋白(LTF)和细胞周期显著相关。鉴定 LN 患者血液、肾小球和肾小管间质中的共同 DEmRNAs 和关键途径为探索疾病的分子机制提供了潜在的研究方向。

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