MicroRNA regulation in renal pathophysiology

Abstract

MicroRNAs are small, noncoding RNA molecules that regulate a considerable amount of human genes on the post-transcriptional level, and participate in many key biological processes. MicroRNA deregulation has been found associated with major kidney diseases. Here, we summarize current knowledge on the role of microRNAs in renal glomerular and tubular pathologies, with emphasis on the mesangial cell and podocyte dysfunction in diabetic nephropathy, the proximal tubular cell survival in acute kidney injury, the transport function of the thick ascending limb in Ca++ imbalance diseases, and the regulation of salt, K+ and blood pressure in the distal tubules. Identification of microRNAs and their target genes provides novel therapeutic candidates for treating these diseases. Manipulation of microRNA function with its sense or antisense oligonucleotide enables coordinated regulation of the entire downstream gene network, which has effectively ameliorated several renal disease phenotypes. The therapeutic potentials of microRNA based treatments, though promising, are confounded by major safety issues related to its target specificity, which remain to be fully elucidated.