Kiyanpour Farnoush, Abedi Maryam, Gheisari Yousof
Department of Bioinformatics, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Res Med Sci. 2023 May 29;28:43. doi: 10.4103/jrms.jrms_702_22. eCollection 2023.
Diabetic kidney disease has substantial burden and limited therapeutic options. An inadequate understanding of the complex gene regulatory circuits underlying this disorder contributes to the insufficiency of current treatment strategies. MicroRNAs (miRNAs) play a crucial role as regulators of functionally related gene networks. Previously, mmu-mir-802-5p was identified as the sole dysregulated miRNA in both the kidney cortex and medulla of diabetic mice. This study aims to investigate the role of miR-802-5p in diabetic kidney disease.
The validated and predicted targets of miR-802-5p were identified using miRTarBase and TargetScan databases, respectively. The functional role of this miRNA was inferred using gene ontology enrichment analysis. The expression of miR-802-5p and its selected targets were assessed by qPCR. The expression of the angiotensin receptor (Agtr1a) was measured by ELISA.
miR-802-5p exhibited dysregulation in both the kidney cortex and medulla of diabetic mice, with two- and four-fold over-expressions, respectively. Functional enrichment analysis of the validated and predicted targets of miR-802-5p revealed its involvement in the renin-angiotensin pathway, inflammation, and kidney development. Differential expression was observed in the Pten transcript and Agtr1a protein among the examined gene targets.
These findings suggest that miR-802-5p is a critical regulator of diabetic nephropathy in the cortex and medulla compartments, contributing to disease pathogenesis through the renin-angiotensin axis and inflammatory pathways.
糖尿病肾病负担沉重且治疗选择有限。对该疾病潜在的复杂基因调控回路认识不足导致了当前治疗策略的不足。微小RNA（miRNA）作为功能相关基因网络的调节因子发挥着关键作用。此前，mmu - mir - 802 - 5p被确定为糖尿病小鼠肾皮质和髓质中唯一失调的miRNA。本研究旨在探讨miR - 802 - 5p在糖尿病肾病中的作用。
分别使用miRTarBase和TargetScan数据库鉴定miR - 802 - 5p的已验证和预测靶点。通过基因本体富集分析推断该miRNA的功能作用。采用qPCR评估miR - 802 - 5p及其选定靶点的表达。通过ELISA检测血管紧张素受体（Agtr1a）的表达。
miR - 802 - 5p在糖尿病小鼠的肾皮质和髓质中均表现出失调，分别有两倍和四倍的过表达。对miR - 802 - 5p的已验证和预测靶点进行功能富集分析，发现其参与肾素 - 血管紧张素途径、炎症和肾脏发育。在所检测的基因靶点中，Pten转录本和Agtr1a蛋白存在差异表达。
这些发现表明miR - 802 - 5p是糖尿病肾病皮质和髓质部分的关键调节因子，通过肾素 - 血管紧张素轴和炎症途径促进疾病发病机制。
