Transcriptomic analysis of differential expression and correlation of coding and non-coding RNAs in urine from patients with idiopathic membranous nephropathy.

IF 5.5 2区生物学 Q1 BIOLOGY

Biology Direct Pub Date : 2026-06-16 DOI:10.1186/s13062-026-00864-7

Jingwen Li, Zhelun Zhou, Rong Wu, Qi Chen

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引用次数: 0

Abstract

Background: The incidence rate of idiopathic membranous nephropathy (IMN) has been increasing, and its pathogenesis is still unclear. Exploring new diagnostic molecular markers and the molecular mechanisms of IMN.

Methods: Fifteen healthy controls and fifteen IMN patients were recruited. Clinical baseline data of all participants, including age, gender, and body mass index (BMI), along with histopathological staging (Ehrenreich-Churg classification) and immunohistochemical staining results for phospholipase A2 receptor (PLA2R), were collected and analyzed. Meanwhile, peripheral blood and urine samples were obtained to detect renal function-related biochemical indicators, including serum creatinine (Scr), estimated glomerular filtration rate (eGFR), serum albumin, 24-hour urinary protein (24 h UPT), serum total cholesterol (TC), anti-PLA2R antibody titer, and serum immunoglobulin G (IgG). Urine samples (n = 10) were also used for high-throughput sequencing analysis.

Results: Serum albumin was significantly downregulated in the IMN group, while 24 h UPT, TC, anti-PLA2R Ab titer, and IgG were upregulated. MicroRNA (miRNA) transcriptomic analysis identified 34 differentially expressed (DE) miRNAs. Hsa-miR-576-3p, hsa-miR-766-5p, and NovelmiRNA-837 exhibited strong diagnostic potential via ROC curve analysis (AUC > 0.8). Sixty-four DE mRNAs were identified in IMN tissues, with enrichment in pathways such as Ribosome and MAPK signaling-fly. ENST00000481739 (RXRA) was upregulated in IMN, correlated with anti-PLA2R Ab titer, and exhibited diagnostic potential (AUC = 0.929). Thirty-five DE lncRNAs were identified in IMN, enriched in autophagy, mitophagy, and apoptosis pathways. TCONS_00180924, TCONS_00176280, TCONS_00208611 correlated significantly with TC, 24-h urinary protein, and anti-PLA2R Ab titer.

Conclusions: This study provides a foundation for developing non-invasive diagnostic tools and targeted therapies for IMN.

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特发性膜性肾病患者尿液中编码和非编码rna差异表达及相关性的转录组学分析。

背景：特发性膜性肾病（IMN）的发病率呈上升趋势，其发病机制尚不清楚。探索新的诊断分子标记和IMN的分子机制。方法：选取15例健康对照和15例IMN患者。收集并分析所有参与者的临床基线数据，包括年龄、性别和体重指数（BMI），以及组织病理学分期（Ehrenreich-Churg分类）和磷脂酶A2受体（PLA2R）的免疫组织化学染色结果。同时采集外周血和尿样，检测肾功能相关生化指标，包括血清肌酐（Scr）、肾小球滤过率（eGFR）、血清白蛋白、24小时尿蛋白（24 h UPT）、血清总胆固醇（TC）、抗pla2r抗体滴度、血清免疫球蛋白G （IgG）。尿液样本（n = 10）也用于高通量测序分析。结果：IMN组血清白蛋白明显下调，24 h UPT、TC、抗pla2r抗体滴度、IgG均上调。MicroRNA （miRNA）转录组学分析鉴定出34个差异表达（DE） miRNA。通过ROC曲线分析，Hsa-miR-576-3p、hsa-miR-766-5p和NovelmiRNA-837显示出较强的诊断潜力（AUC >.8）。在IMN组织中鉴定出64种DE mrna，富集于核糖体和MAPK信号通路。ENST00000481739 （RXRA）在IMN中表达上调，与抗pla2r抗体滴度相关，具有诊断潜力（AUC = 0.929）。在IMN中鉴定出35个DE lncrna，富集于自噬、有丝自噬和凋亡途径。tcon_00180924、tcon_00176280、tcon_00208611与TC、24小时尿蛋白、抗pla2r抗体滴度显著相关。结论：本研究为开发IMN的无创诊断工具和靶向治疗提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology Direct 生物-生物学

CiteScore

6.40

自引率

10.90%

发文量

审稿时长

7 months

期刊介绍： Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.