Identification of genes involved in the development of diabetic nephropathy and their miRNA-induced regulation. In silico analysis.

Abstract

Introduction. Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. It is characterized by pathological albumin excretion greater than 300 mg/dL/24 h, hyperglycemia, and high blood pressure. Accurate diagnosis of this disease requires histological analysis of renal biopsies, where sufficient samples are usually not obtained for repeated procedures. Therefore, in recent years, various biomolecules have been proposed for the timely identification and accurate diagnosis of multiple diseases, including DN. In recent years, miRNAs have been shown to play a crucial role in the development of various diseases. miRNAs are small, non-coding RNAs that regulate gene expression post-transcriptionally and have been proposed as potential therapeutic agents for diseases such as cardiometabolic disorders, bone metabolism disorders, various types of cancer, and diabetes. Objective. Therefore, in this work, miRNAs and their respective target genes associated with DN were identified through in silico analysis. Methodology. To identify miRNAs, a data search was conducted using whole-genome analysis technologies such as expression microarrays. Files were retrieved in CEL format, data was normalized, and differential expression analysis was performed. The target genes of each selected miRNA were subsequently identified and analyzed to determine the signaling pathways in which they are involved using the KEGG pathway tool. Results. Three miRNAs associated with DN were identified, of which these three miRNAs regulate 57 genes and participate in 7 KEGG signaling pathways related to DN and chronic kidney disease. These data allowed the generation of a network representing the interaction between miRNAs and genes. Conclusions. Alterations in the expression profiles of miRNAs and target genes can affect multiple biological processes and lead to the development of DN. Therefore, miRNAs and genes involved in the development of DN could be of clinical interest as potential biomarkers or molecules for the diagnosis and monitoring of the disease. Finally, this analysis uses standardized methods for searching for miRNA target genes and microarray analysis, allowing these results to be replicated.