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尿外泌体miR-136-5p在糖尿病肾病中的表达及其临床诊断价值评估

Expression of urinary exosomal miR-136-5p in diabetic kidney disease and evaluation of its clinical diagnostic value.

作者信息

Zheng Shanshan, Li Jiao, Ma Chaoqun, Wang Baobao, Lin Sen, Wang Zunsong, Li Wenbin, Wang Ping, Chen Ping, Li Hao, Wu Jing, Liu Yipeng

机构信息

Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People's Republic of China.

Shandong Institute of Nephrology, Jinan, People's Republic of China.

出版信息

Sci Rep. 2025 Jul 4;15(1):23897. doi: 10.1038/s41598-025-06810-3.

Abstract

Diabetic kidney disease (DKD) has become a major cause of chronic kidney disease and end-stage renal disease. Numerous studies have indicated that exosomal miRNAs play a crucial role in the pathophysiological processes of DKD. We screened differentially expressed miRNAs in urinary exosomes from patients with DKD using the GEO database and performed PCR validation both in patients who were pathologically diagnosed and clinically diagnosed. We assessed the clinical diagnostic value of urinary exosomal miRNAs using ROC curves, analyzed the correlation between miRNAs and clinical indicators, predicted the target genes using the miRTarBase database and explored the potential signaling pathways involved through functional enrichment analysis. Screening results showed that the expression of miR-136-5p was significantly elevated in the DKD group compared to the DM group, with significance maintained in validation samples. The sensitivity and specificity of miR-136-5p for diagnosing DKD were 72.2% and 78.4%, respectively, with an area under the curve of 0.722. Additionally, the expression of miR-136-5p was positively correlated with UACR, urea nitrogen, cystatin C, chronic kidney disease progression risk stratification indicators, and negatively correlated with eGFR. 152 target genes of miR-136-5p were predicted and enriched in 25 pathways, including insulin secretion, cAMP signaling pathway, and sphingolipid signaling pathway.

摘要

糖尿病肾病(DKD)已成为慢性肾脏病和终末期肾病的主要病因。大量研究表明,外泌体微小RNA(miRNAs)在DKD的病理生理过程中起关键作用。我们利用基因表达综合数据库(GEO数据库)筛选了DKD患者尿外泌体中差异表达的miRNAs,并在病理诊断和临床诊断的患者中进行了聚合酶链反应(PCR)验证。我们使用受试者工作特征曲线(ROC曲线)评估了尿外泌体miRNAs的临床诊断价值,分析了miRNAs与临床指标之间的相关性,利用miRTarBase数据库预测了靶基因,并通过功能富集分析探索了相关的潜在信号通路。筛选结果显示,与糖尿病(DM)组相比,DKD组中miR-136-5p的表达显著升高,且在验证样本中仍具有显著性差异。miR-136-5p诊断DKD的敏感性和特异性分别为72.2%和78.4%,曲线下面积为0.722。此外,miR-136-5p的表达与尿白蛋白肌酐比值(UACR)、尿素氮、胱抑素C、慢性肾脏病进展风险分层指标呈正相关,与估算肾小球滤过率(eGFR)呈负相关。预测出miR-136-5p的152个靶基因,并富集于25条信号通路中,包括胰岛素分泌、环磷酸腺苷(cAMP)信号通路和鞘脂信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/12227711/c72203c01c31/41598_2025_6810_Fig1_HTML.jpg

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