%0 Journal Article
%T MicroRNA in Diabetic Nephropathy: Renin Angiotensin, AGE/RAGE, and Oxidative Stress Pathway
%A Shinji Hagiwara
%A Aaron McClelland
%A Phillip Kantharidis
%J Journal of Diabetes Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/173783
%X MicroRNAs (miRNA) are a novel class of small, noncoding RNA molecules that have gained the attention of many researchers in recent years due to their ability to posttranscriptionally regulate the expression of families of genes simultaneously. Their role in normal physiology and pathobiology is intriguing and their regulation in normal and disease states is fascinating. That the cells can return to a state of homeostasis when these small molecules are perturbed is truly remarkable given the multiple cellular targets of each miRNA and that many mRNAs are targeted by multiple miRNAs. Several reviews have covered aspects of miRNA function in biology and disease. Here, we review the role of miRNA in regulating the renin-angiotensin system, AGE/RAGE signalling, and under conditions of oxidative stress in the context of diabetic nephropathy. 1. Introduction The World Health Organization states that ~347 million people, roughly 9.5% of the adult population, were suffering from diabetes in 2008 [1]. The incidence of diabetes is rapidly increasing with estimates suggesting that this number will almost double by 2030. Diabetes mellitus is a major cause of chronic kidney disease (CKD) worldwide and is associated with enhanced morbidity and mortality, in particular accelerated cardiovascular disease [2, 3]. Diabetic nephropathy (DN) is now the most common cause of end-stage renal failure in the Western world [4]. Clinical associations that frequently precede overt DN are hypertension and poor glycaemic control [5], although a subset of patients develop nephropathy despite the proper glycemic control [6] and normal blood pressure. Once nephropathy is established, blood pressure often rises further, but glycaemic control can paradoxically improve as a result of reduced renal insulin clearance [7]. It is postulated that the interplay between metabolic and hemodynamic pathways plays an important role in the development and progression of DN [8] (Figure 1). Increased systemic and intraglomerular pressure is associated with increased albuminuria and glomerular injury. Activation of the renin-angiotensin-aldosterone system (RAAS) has been recognized as a key component of DN progression. Additionally, chronic hyperglycemia promotes the generation of advanced glycation end-products (AGEs). It is widely accepted that AGEs mediate their effects both directly and indirectly through receptor-dependent mechanisms. The receptor for AGE (RAGE) acts as a signal transduction receptor, and the RAGE-AGE interaction activates multiple intracellular signalling pathways which increase
%U http://www.hindawi.com/journals/jdr/2013/173783/