Department of Endocrinology, The Second Medical Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Front Endocrinol (Lausanne). 2023 Feb 21;14:1144331. doi: 10.3389/fendo.2023.1144331. eCollection 2023.
To explore biomarkers of diabetic nephropathy (DN) and predict upstream miRNAs.
The data sets GSE142025 and GSE96804 were obtained from Gene Expression Omnibus database. Subsequently, common differentially expressed genes (DEGs) of renal tissue in DN and control group were identified and protein-protein interaction network (PPI) was constructed. Hub genes were screened from in DEGs and made an investigation on functional enrichment and pathway research. Finally, the target gene was selected for further study. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of target gene and predicted its upstream miRNAs.
130 common DEGs were obtained through analysis, and 10 Hub genes were further identified. The function of Hub genes was mainly related to extracellular matrix (ECM), collagen fibrous tissue, transforming growth factor (TGF) -β, advanced glycosylation end product (AGE) -receptor (RAGE) and so on. Research showed that the expression level of Hub genes in DN group was significantly higher than that in control group. (all P<0.05). The target gene matrix metalloproteinase 2 (MMP2) was selected for further study, and it was found to be related to the fibrosis process and the genes regulating fibrosis. Meanwhile, ROC curve analysis showed that MMP2 had a good predictive value for DN. miRNA prediction suggested that miR-106b-5p and miR-93-5p could regulate the expression of MMP2.
MMP2 can be used as a biomarker for DN to participate in the pathogenesis of fibrosis, and miR-106b-5p and miR-93-5p may regulate the expression of MMP2 as upstream signals.
探索糖尿病肾病（DN）的生物标志物并预测上游 miRNA。
从基因表达综合数据库中获取 GSE142025 和 GSE96804 数据集。然后，鉴定 DN 组和对照组肾组织中的共同差异表达基因（DEGs），并构建蛋白质-蛋白质相互作用网络（PPI）。从 DEGs 中筛选出枢纽基因，并对其进行功能富集和通路研究。最后，选择靶基因进行进一步研究。使用受试者工作特征（ROC）曲线评估靶基因的诊断效率，并预测其上游 miRNA。
通过分析获得了 130 个共同 DEGs，并进一步鉴定出 10 个枢纽基因。枢纽基因的功能主要与细胞外基质（ECM）、胶原纤维组织、转化生长因子（TGF）-β、晚期糖基化终产物（AGE）-受体（RAGE）等有关。研究表明，DN 组中枢纽基因的表达水平明显高于对照组（均 P<0.05）。选择靶基因基质金属蛋白酶 2（MMP2）进行进一步研究，发现其与纤维化过程和调节纤维化的基因有关。同时，ROC 曲线分析表明 MMP2 对 DN 具有良好的预测价值。miRNA 预测表明，miR-106b-5p 和 miR-93-5p 可以调节 MMP2 的表达。
MMP2 可作为 DN 的生物标志物，参与纤维化的发病机制，miR-106b-5p 和 miR-93-5p 可能作为上游信号调节 MMP2 的表达。
