Review: The role of microRNAs in kidney disease

Abstract

SUMMARY AT A GLANCEThis is a comprehensive and scholarly review of the current knowledge of microRNAs (miRNAs) in renal disease. MiRNAs are emerging as important regulators of disease processes. Understanding how miRNAs modulate pathogenetic pathways is important, as therapeutic manipulation of miRNAs may evolve as a potential strategy for treating renal diseases in the future. ABSTRACT:MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocytespecific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-b activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future. INTRODUCTIONMicroRNAs (miRNAs) are endogenous non-coding RNA molecules, 20-22 nucleotides in length. The discovery and characterization of miRNA in the last decade is revolutionizing our understanding of gene regulation, cell differentiation, proliferation, apoptosis, metabolism and pathophysiology of many diseases including kidney diseases. The understanding of miRNA biology and its role in various diseases is still in its early stage but is expanding rapidly. The aim of this review is to highlight miRNA biology in relation to kidney diseases and its importance in understanding disease mechanisms. Future directions in this field will also be discussed. DISCOVERY AND BIOGENESIS OF MICRORNAsMiRNAs were first found in the nematode Caenorhabditis elegans in 1993.1 Since then they have also been described widely in plants and mammals. 2 MiRNAs are first transcribed in the nucleus as stem-loop primary miRNA, which are then cleaved into shorter precursor miRNA by Drosha, an RNase III, and its essential cofactor called DGCR8 (DiGeorge syndrome critical region 8), a double-stranded RNA-binding protein (Fig. 1). [3][4][5][6] The precursor miRNAs are tran...

microRNAs in Diabetic Kidney Disease

“…There are also emerging reports about microRNAs in renal field. Several comprehensive reviews of microRNAs research on kidney development, function, and diseases have been previously published [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. This review will focus on the current research progress of microRNAs in diabetic kidney disease.…”

“…In renal research, more evidence demonstrate that specific microRNAs alter renal physiology by changing expression patterns, mediating actions of TGFon renal fibrosis, affecting normal functions of MC, TEC, and podocyte, and inducing ECM deposition, podocyte dysfunction, and albuminuria during renal diseases [24,28,33,34]. However, how microRNAs exactly mediate the diabetic renal injury is underexplored.…”

Circulating microRNAs as novel biomarkers for dilated cardiomyopathy

“…Because miRNAs are normally excreted by the kidney [17], it is possible that miRNA levels in the plasma are affected by renal function. To assess whether such an effect may have caused a bias in our study, we compared the miRNA levels between DCM patients whose values for the eGFR were above the median and the samples with values that were below the median.…”

Urinary Exosomes for Protein Biomarker Research

“…Urinary exosomes seem to be particularly rich in miRNAs too. The use of miRNA as diagnostic biomarkers in exosome research is an emerging field due to important potential advantages over standard mRNA (Li et al, 2010). There are over a thousand proteins identified from UE preparations published in the Exocarta ) and the Urinary Exosome Protein Database (Pisitkun et al, 2004) including the six exosome markers commonly used in exosome research (Alix, Tsg101, CD63, CD9, CD81, HSP70).…”