MicroRNAs are potential therapeutic targets in fibrosing kidney disease: lessons from animal models

Publication date: Autumn 2013 Source:Drug Discovery Today: Disease Models, Volume 10, Issue 3 Author(s): Jeremy S. Duffield , Monica Grafals , Didier Portilla Chronic disease of the kidneys has reached epidemic proportions in industrialized nations. New therapies are urgently sought. Using a combination of animal models of kidney disease and human biopsy samples, a pattern of dysregulated microRNA expression has emerged which is common to chronic diseases. Several of these dysregulated microRNAs have recently been shown to have functional consequences for the disease process and therefore may be potential therapeutic targets. We highlight microRNA-21, the most comprehensively studied microRNA in the kidney so far. MicroRNA-21 is expressed widely in healthy kidney but studies from knockout mice indicate it is largely inert. Although microRNA-21 is upregulated in many cell compartments including leukocytes, epithelial cells and myofibroblasts, the inert microRNA-21 also appears to become activated, by unclear mechanisms. Mice lacking microRNA-21 are protected from kidney injury and fibrosis in several distinct models of kidney disease, and systemically administered oligonucleotides that specifically bind to the active site in microRNA-21, inhibiting its function, recapitulate the genetic deletion of microRNA-21, suggesting that inhibitory oligonucleotides may have therapeutic potential. Recent studies of microRNA-21 targets in kidney indicate that it normally functions t...
Source: Drug Discovery Today: Disease Models - Category: Drugs & Pharmacology Source Type: research