MicroRNAs are potential therapeutic targets in fibrosing XXXX : lessons from animal models.

@entity1 @entity8 @entity82 @entity844 @entity19 @entity26 @entity102 @entity740 @entity766
@entity740 has reached epidemic proportions in industrialized nations. New therapies are urgently sought. Using a combination of animal models of @entity8 and @entity1 biopsy samples, a pattern of dysregulated microRNA expression has emerged which is common to @entity102 . A number of these dysregulated microRNA have recently been shown to have functional consequences for the disease process and therefore may be potential therapeutic targets. We highlight @entity766 , the most comprehensively studied microRNA in the kidney so far. @entity766 is expressed widely in healthy kidney but studies from knockout @entity19 indicate it is largely inert. Although @entity766 is upregulated in many cell compartments including leukocytes, epithelial cells and myofibroblasts, the inert @entity766 also appears to become activated, by unclear mechanisms. @entity19 lacking @entity766 are protected from @entity8 and @entity82 in several distinct models of @entity8 , and systemically administered oligonucleotides that specifically bind to the active site in @entity766 , inhibiting its function, recapitulate the genetic deletion of @entity766 , suggesting inhibitory oligonucleotides may have therapeutic potential. Recent studies of @entity766 targets in kidney indicate that it normally functions to silence metabolic pathways including @entity844 metabolism and pathways that prevent Reactive @entity26 Species generation in peroxisomes and mitochondria in epithelial cells and myofibroblasts. Targeting specific pathogenic microRNAs in a specific manner is feasible in vivo and may be a new therapeutic target in disease of the kidney.
