MPO-ANCA相关性血管炎患者血浆外泌体mRNA表达谱的特征性变化及其与发病机制的可能相关性

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Yangfan Chen, Dongqing Zhou, Xin Qian, Shangqing Ge, Zongwen Shuai
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引用次数: 0

摘要

探索髓过氧化物酶特异性抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(MPO-AAV)患者外泌体中mRNA的表达模式和潜在作用。从MPO-AAV患者和健康对照组(HCs)分离血浆外泌体,通过外泌体mRNA测序筛选不同的mRNA表达。通过生物信息学分析,对两组患者外泌体中差异表达的 mRNA 进行了比较研究。通过实时定量聚合酶链反应(RT-qPCR),筛选出六种表达差异最大的 mRNA,并在更大的 MPO-AAV 患者和 HCs 群体中进行了验证。对这些选定的 mRNA 与患者特征之间的关系进行了统计分析。与 HC 相比,MPO-AAV 患者外泌体中共有 1077 个 mRNA 被显著上调,其中包括 DEPDC1B 和 TPST1,而 NSUN4 和 AK4 则被显著下调。统计分析未发现所选的六种 mRNA 与疾病活动性等临床指标之间存在任何相关性。GO 富集分析显示,这些差异表达基因参与了各种酶活性、蛋白质合成等。KEGG 通路分析显示,代谢通路、细胞粘附分子、上皮细胞信号转导和丝裂原活化蛋白激酶(MAPK)信号转导通路在外泌体 mRNA 中明显富集。MPO-AAV患者和HC之间的外泌体mRNA表达存在明显差异,这可能与MPO-AAV的发生和发展有关。这些发现为进一步研究MPO-AAV的发病机制和确定新的潜在治疗靶点提供了线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis

Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis

To explore the expression patterns and potential roles of mRNAs in exosomes from patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV). Plasma exosomes were isolated from MPO-AAV patients and healthy controls (HCs) to screen for differential mRNA expression via exosomal mRNA sequencing. The differentially expressed mRNAs in exosomes from the 2 groups were comparatively explored by bioinformatics analysis. The six most differentially expressed mRNAs were selected and validated in larger groups of MPO-AAV patients and HCs by real-time quantitative polymerase chain reaction (RT‒qPCR). The relationships between these selected mRNAs and patient characteristics were statistically analyzed. Compared with HCs, a total of 1077 mRNAs in exosomes from MPO-AAV patients were found to be significantly upregulated, including DEPDC1B and TPST1, while NSUN4 and AK4 were significantly downregulated. Statistical analysis did not reveal any correlation between the six selected mRNAs and clinical indicators, including disease activity. GO enrichment analysis revealed that these differentially expressed genes participate in various enzyme activities, protein synthesis, etc. KEGG pathway analysis revealed that metabolic pathways, cell adhesion molecules, epithelial signaling, and mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched in the exosomal mRNAs. There were significant differences in the expression of exosomal mRNAs between MPO-AAV patients and HCs, which may be related to the occurrence and development of MPO-AAV. These findings provide clues for further investigations of MPO-AAV pathogenesis and the identification of new potential therapeutic targets.

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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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