MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets

MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms and thereby affect many cellular processes and disease states. Over 2,000 human mature miRNAs have been identified, and at least 60% of all human protein-coding genes are known to be regulated by miRNAs. MicroRNA biogenesis involves classical transcription regulation and processing by key ribonucleases, as well as other protein factors and epigenetic mechanisms. Diabetic nephropathy (DN), a severe microvascular complication frequently associated with diabetes mellitus, is a major cause of renal failure. Although several mechanisms of regulation of key renal genes implicated in DN pathogenesis have been identified, a greater understanding is needed to develop better treatment modalities. Recent studies show that miRNAs induced in renal cells in vivo and in vitro under diabetic conditions can promote the accumulation of extracellular matrix proteins related to fibrosis and glomerular dysfunction. In this review, we highlight the significance of the expression of miRNAs in various stages of DN and emerging approaches to exploit them as biomarkers for early detection or novel therapeutic targets to prevent progression of DN.