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IgA血管炎肾病患儿尿外泌体miRNA-mRNA网络的构建及诊断效能评估

Construction and diagnostic efficacy assessment of the urinary exosomal miRNA-mRNA network in children with IgA vasculitis nephritis.

作者信息

Zhang Yunfan, Yang Huanhuan, Chen Yi, Tang Yuxian, Chen Junyan, Huang Jun, Feng Ai, Weng Zengfeng, Li Fenrong, Lin Jinfeng, Xie Jingqi, Zhang Chunfang, Chen Jie, Gao Chunlin, Nie Xiaojing

机构信息

Department of Pediatrics, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China.

Department of Pediatrics, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, China.

出版信息

FASEB J. 2025 Apr 15;39(7):e70492. doi: 10.1096/fj.202403111R.

Abstract

This study aimed to comprehensively evaluate the diagnostic potential of urinary exosomal microRNA (miRNA) in IgA vasculitis (IgAV) kidney injury by meticulously comparing the miRNA expression profiles in urine exosomes between children diagnosed with IgAV and those with IgA vasculitis nephritis (IgAVN). Urine samples were obtained from children with IgAV who were treated at our hospital from October 2022 to October 2023. These samples were then categorized into the IgAV group and the IgAVN group. High-throughput sequencing and bioinformatics analysis techniques were employed to conduct a thorough analysis of the differentially expressed miRNAs between the two groups. Additionally, the correlation between urinary exosomal miRNA and clinical parameters was evaluated. A total of 57 urinary exosomal miRNAs exhibited differential expression between the IgAV and IgAVN groups. Specifically, in the IgAVN group, 42 miRNAs were upregulated, while 15 were downregulated. Lasso regression analysis and ROC analysis identified five candidate urinary exosomal miRNAs with high diagnostic accuracy. A prediction of 95 target genes related to the candidate miRNAs led to the construction of an exosomal miRNA-mRNA regulatory network consisting of four key miRNAs and ten hub genes. Gene function and metabolic pathway analyses indicated that these ten hub genes were predominantly enriched in pro-fibrotic and inflammatory pathways. The analysis incorporating clinical parameters demonstrated a significant correlation between hsa-miR-383-5p and urinary protein levels. This research identified exosomal miRNAs and mRNAs with differential expression patterns associated with IgAVN and constructed the corresponding exosomal miRNA-mRNA network. It was determined that hsa-miR-3065-5p, hsa-miR-383-5p, hsa-miR-25-3p, and hsa-miR-450b-5p might mediate the pathogenesis of IgAVN by targeting pro-fibrotic and inflammatory pathways. Among them, exosomal hsa-miR-383-5p is highly likely to serve as a novel non-invasive biomarker for assessing the disease status of IgAVN, thereby offering new perspectives on the non-invasive diagnosis and treatment of IgAVN.

摘要

本研究旨在通过细致比较诊断为IgA血管炎(IgAV)的儿童与IgA血管炎肾炎(IgAVN)儿童尿液外泌体中的微小RNA(miRNA)表达谱,全面评估尿液外泌体miRNA在IgA血管炎肾损伤中的诊断潜力。收集了2022年10月至2023年10月在我院接受治疗的IgAV儿童的尿液样本。这些样本随后被分为IgAV组和IgAVN组。采用高通量测序和生物信息学分析技术对两组之间差异表达的miRNA进行全面分析。此外,还评估了尿液外泌体miRNA与临床参数之间的相关性。IgAV组和IgAVN组之间共有57种尿液外泌体miRNA表现出差异表达。具体而言,在IgAVN组中,42种miRNA上调,15种下调。套索回归分析和ROC分析确定了5种具有高诊断准确性的候选尿液外泌体miRNA。对与候选miRNA相关的95个靶基因进行预测,构建了一个由4个关键miRNA和10个枢纽基因组成的外泌体miRNA - mRNA调控网络。基因功能和代谢途径分析表明,这10个枢纽基因主要富集在促纤维化和炎症途径中。纳入临床参数的分析表明,hsa - miR - 383 - 5p与尿蛋白水平之间存在显著相关性。本研究鉴定了与IgAVN相关的具有差异表达模式的外泌体miRNA和mRNA,并构建了相应的外泌体miRNA - mRNA网络。确定hsa - miR - 3065 - 5p、hsa - miR - 383 - 5p、hsa - miR - 25 - 3p和hsa - miR - 450b - 5p可能通过靶向促纤维化和炎症途径介导IgAVN的发病机制。其中,外泌体hsa - miR - 383 - 5p极有可能作为评估IgAVN疾病状态的新型非侵入性生物标志物,从而为IgAVN的非侵入性诊断和治疗提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/060c/11959522/a11e24c5b51c/FSB2-39-e70492-g002.jpg

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