NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
J Clin Lab Anal. 2020 Dec;34(12):e23549. doi: 10.1002/jcla.23549. Epub 2020 Sep 1.
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.
白蛋白与肌酐比值（ACR）作为糖尿病肾病（DKD）最常见的诊断指标之一，在临床应用中显示出相当有限的预测能力。我们通过分析尿液的微阵列表达谱，寻找用于 DKD 的潜在生物标志物的差异表达 miRNA。
收集 2 型糖尿病（T2DM）患者尿液样本（ACR 为 30mg/g<ACR<300mg/g，DKD 组）或无 DKD（ACR<30mg/g，DM 组），进行 miRNA 微阵列分析。通过生物信息学分析筛选差异表达的 miRNA，并通过定量实时 PCR 进行验证。在 miRDB、Targetscan 和 microRNA.org 数据库中预测差异表达 miRNA 的靶基因。我们还进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）信号通路分析，以探讨 DKD 中的潜在机制。
与 DM 组相比，DKD 组有 9 个 miRNA 下调，17 个 miRNA 上调。与 DM 组相比，DKD 组 miR-3137 和 miR-4270 的水平分别为 0.670±0.505 和 2.116±1.762 倍，差异具有显著意义。miRDB、Targetscan 和 microRNA.org 数据库同时预测了 1076 个靶基因。根据 GO 分析结果，内质网系统紊乱可能是 DKD 的主要病理变化之一。此外，通过 KEGG 分析发现，Rap1 信号通路在 DKD 中也发生了明显改变。
miR-3137 和 miR-4270 具有成为 DKD 尿液生物标志物的潜力。DKD 的病理变化可能与内质网系统紊乱和 Rap1 信号通路改变有关。
