MicroRNAs as mediators and therapeutic targets in chronic kidney disease

Chronic kidney disease (CKD) is characterized by tubulointerstitial deposition of extracellular matrix, tubular atrophy and dilatation; the replacement of organ architecture by connective tissue results in progressive loss of organ function. Micro (mi)RNAs are important mediators of tissue fibrosis under various pathological conditions and are of potential therapeutic relevance. These short, noncoding nucleotides (∼22 bases) regulate target messenger RNAs at the post-transcriptional level. Several hundred miRNAs regulate a considerable amount of the human genome and are involved in virtually all biological processes, including cellular proliferation, apoptosis and differentiation. Thus, miRNA deregulation often results in impaired cellular function and development of disease. Here, we summarize the current knowledge on the role of miRNAs in CKD, with particular emphasis on hypertensive kidney disease, diabetic nephropathy, glomerular biology, and IgA nephropathy. Identification of miRNA regulation and function in renal pathology may pinpoint miRNAs as new therapeutic targets in kidney fibrosis and related diseases. A new class of RNA therapeutics, that is, miRNA modulators (such as antagomirs) have been developed, which enable specific targeting of miRNAs and respective downstream gene networks in vivo, thus influencing the mechanisms that underlie disease initiation or progression. The therapeutic potential of miRNA-based treatment strategies in CKD are discussed.