Urinary miR-3137 and miR-4270 as potential biomarkers for diabetic kidney disease.

Urinary miR-3137 and miR-4270 as potential biomarkers for diabetic kidney disease.
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DOI:
10.1002/jcla.23549
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发表时间:
2020-12
影响因子:
2.7
通讯作者:
Chen L
Chen L
中科院分区:
医学4区
文献类型:
--
作者:
Li X;Xu R;Liu X;Xu L;Xue M;Cheng Y;Li T;Yu X;Wang Y;Li C;Sun B;Chen L

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作为糖尿病肾病(DKD)最常见的诊断指标之一,白蛋白/肌酐比值(ACR)在临床应用中显示出相当有限的预测能力。我们分析了尿液的微阵列表达谱,以寻找差异表达的miRNA作为DKD的潜在生物标志物。收集来自具有(30 mg/g < ACR < 300 mg/g,DKD组)或不具有DKD(ACR < 30 mg/g,DM组)的2型糖尿病(T2 DM)患者的尿液样品用于miRNA微阵列分析。通过生物信息学分析筛选差异表达的miRNAs,并通过定量真实的时间PCR进行验证。在miRDB、Targetscan和microRNA.org数据库中预测差异表达的miRNA的靶基因。我们还进行了基因本体论(GO)和京都基因和基因组百科全书(KEGG)信号通路分析,以探索DKD的潜在机制。与DM组相比,DKD组中有9种miRNAs表达下调,17种miRNAs表达上调。DKD组miR-3137和miR-4270的水平分别是DM组的0.670 ± 0.505和2.116 ± 1.762倍,差异有显著性。miRDB、Targetscan和microRNA.org数据库同时预测了总共1076个靶基因。根据GO分析结果,内膜系统的紊乱可能是DKD的主要病理改变之一。此外,KEGG分析发现Rap 1信号通路在DKD中也有明显改变. miR-3137和miR-4270显示了DKD尿液生物标志物的潜力。DKD的病理变化可能与内膜系统紊乱及Rap 1信号通路改变有关。DKD患者尿液中miR-3137和miR-4270的水平分别是DM组的0.670 ± 0.505和2.116 ± 1.762倍,显示了DKD尿液生物标志物的潜力。DKD的病理变化可能与内膜系统紊乱和Rap 1信号通路的改变有关。
As one of the most prevalent diagnostic indicators of diabetic kidney disease (DKD), albumin‐to‐creatinine ratio (ACR) shows considerably limited predictive power in clinical application. We analyzed microarray expression profiling of urine to seek for differentially expressed miRNAs for potential biomarkers of DKD. Urine samples from type 2 diabetes mellitus (T2DM) patients with (30 mg/g < ACR < 300 mg/g, DKD group) or without DKD (ACR < 30 mg/g, DM group) were collected for miRNA microarray analysis. The differentially expressed miRNAs were screened by bioinformatics analysis and validated by quantitative real‐time PCR. Target genes of differentially expressed miRNAs were predicted in miRDB, Targetscan, and microRNA.org databases. We also conducted the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways analysis to explore for potential mechanisms in DKD. Nine miRNAs were down‐regulated and seventeen miRNAs were up‐regulated in DKD group, compared to DM group. The levels of miR‐3137 and miR‐4270 in DKD group were 0.670 ± 0.505 and 2.116 ± 1.762 times than those in DM group, respectively, showing great significance. A total of 1076 target genes were simultaneously predicted by miRDB, Targetscan, and microRNA.org databases. According to the GO analysis results, disorders of endomembrane system may be one of the major pathological changes in DKD. In addition, Rap 1 signaling pathway is also altered obviously in DKD, discovered by the KEGG analysis. MiR‐3137 and miR‐4270 show the potential for urinary biomarkers of DKD. The pathological changes of DKD may be related to disorders of endomembrane system and alternation of Rap1 signaling pathway. The levels of miR‐3137 and miR‐4270 in urine of DKD patients were 0.670 ± 0.505 and 2.116 ± 1.762 times than those in DM group, showing the potential for urinary biomarkers of DKD. The pathological changes of DKD may be related to disorders of endomembrane system and alternation of Rap1 signaling pathway.
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