Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China (mainland).
Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China (mainland).
Med Sci Monit. 2019 Mar 13;25:1903-1916. doi: 10.12659/MSM.913057.
BACKGROUND To identify noninvasive diagnostic biomarkers for membranous nephropathy (MN). MATERIAL AND METHODS The mRNA microarray datasets GSE73953 using peripheral blood mononuclear cells (PBMCs) of 8 membranous nephropathy patients and 2 control patients; and microRNAs (miRNA) microarray dataset GSE64306 using urine sediments of 4 membranous nephropathy patients and 6 control patients were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were respectively identified from PBMCs and urine sediments of membranous nephropathy patients, followed with functional enrichment analysis, protein-protein interaction (PPI) analysis, and miRNA-target gene analysis. Finally, the DEGs and the target genes of DEMs were overlapped to obtain crucial miRNA-mRNA interaction pairs for membranous nephropathy. RESULTS A total of 1246 DEGs were identified from PBMCs samples, among them upregulated CCL5 was found to be involved in the chemokine signaling pathway, and BAX was found to be apoptosis related; while downregulated PPM1A and CDK1 were associated with the MAPK signaling pathway and the p53 signaling pathway, respectively. The hub role of CDK1 (degree=18) and CCL5 (degree=12) were confirmed after protein-protein interaction network analysis in which CKD1 could interact with RAB1A. A total of 28 DEMs were identified in urine sediments. The 276 target genes of DEMs were involved in cell cycle arrest (PPM1A) and intracellular signal transduction (BRSK1). Thirteen genes were shared between the DEGs in PMBCs and the target genes of DEMs in urine sediments, but only hsa-miR-192-3p-RAB1A, hsa-miR-195-5p-PPM1A, and hsa-miR-328-5p-BRSK1 were negatively related in their expression level. CONCLUSIONS Both peripheral blood and urinary miR-195-5p, miR-192-3p, miR-328-5p, and their target genes PPM1A, RAB1A, and BRSK1 may be potential biomarkers for membranous nephropathy by participating in inflammation and apoptosis.
为了鉴定膜性肾病（MN）的非侵入性诊断生物标志物。
从基因表达综合数据库中下载了使用 8 例膜性肾病患者和 2 例对照患者外周血单个核细胞（PBMC）的 mRNA 微阵列数据集 GSE73953；和使用 4 例膜性肾病患者和 6 例对照患者尿液沉淀物的 microRNAs（miRNA）微阵列数据集 GSE64306。分别从膜性肾病患者的 PBMC 和尿液沉淀物中鉴定差异表达基因（DEGs）和差异表达 miRNAs（DEMs），然后进行功能富集分析、蛋白质-蛋白质相互作用（PPI）分析和 miRNA-靶基因分析。最后，将 DEGs 和 DEMs 的靶基因重叠，以获得膜性肾病的关键 miRNA-mRNA 相互作用对。
从 PBMCs 样本中鉴定出了 1246 个 DEGs，其中上调的 CCL5 被发现参与趋化因子信号通路，BAX 被发现与凋亡有关；而下调的 PPM1A 和 CDK1 分别与 MAPK 信号通路和 p53 信号通路有关。蛋白质-蛋白质相互作用网络分析证实了 CDK1（度=18）和 CCL5（度=12）的枢纽作用，其中 CDK1 可以与 RAB1A 相互作用。在尿液沉淀物中鉴定出了 28 个 DEM。DEMs 的 276 个靶基因参与细胞周期停滞（PPM1A）和细胞内信号转导（BRSK1）。PMBCs 中的 DEGs 和尿液沉淀物中 DEMs 的靶基因之间有 13 个基因共享，但只有 hsa-miR-192-3p-RAB1A、hsa-miR-195-5p-PPM1A 和 hsa-miR-328-5p-BRSK1 的表达水平呈负相关。
外周血和尿液中的 miR-195-5p、miR-192-3p、miR-328-5p 及其靶基因 PPM1A、RAB1A 和 BRSK1 可能通过参与炎症和凋亡成为膜性肾病的潜在生物标志物。
