RNA expression signatures and posttranscriptional regulation in diabetic nephropathy

In the last decade, the integration of molecular approaches including transcriptome and miRNome analyses uncovered pathological mechanisms involved in the progression of diabetic nephropathy (DN). Using these techniques, molecular marker candidates [both messenger RNA (mRNA) and miRNA] have also been identified which may enable the characterization of patients at high risk for progression to end-stage renal disease. The results of such studies are urgently needed for a molecular definition of DN and for targeted treatment to improve patient care. The heterogeneity of kidney tissue and the minute amounts of RNA isolated from renal biopsies remain a challenge for omics-studies. Nevertheless, several studies have succeeded in the identification of RNA expression signatures in patients with diabetes and kidney disease. These studies show a reduced expression of growth factors such as VEGF and EGF, and an increased expression of matrix components and matrix-modulating enzymes, an activation of specific NF-κB modules, inflammatory pathways and the complement system. microRNAs are involved in the fine-tuning of mRNA abundance by binding to the 3' untranslated region of a target mRNA, which leads in most cases to translational repression or mRNA cleavage and a decrease in protein output. Here, we review the platforms used for miRNA expression profiling and ways to predict miRNA targets and functions. Several miRNAs have been shown to be involved in the pathogenesis of DN (e.g. miR-21, miR-192, miR-215, miR-216a, miR-29, let-7, miR-25, miR-93, etc.). Functional studies provide evidence that miRNAs are not only diagnostic tools but also represent potential therapeutic targets in DN.