MicroRNAs as mediators and therapeutic targets in chronic kidney disease

Abstract

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.

FOG2 Protein Down-regulation by Transforming Growth Factor-β1-induced MicroRNA-200b/c Leads to Akt Kinase Activation and Glomerular Mesangial Hypertrophy Related to Diabetic Nephropathy

“…miRNAs are a group of endogenously produced, short noncoding RNAs that bind to the 3ЈUTRs of target mRNAs through base pairing and inhibit mRNA translation or promote mRNA degradation (20,21). Several miRNAs expressed in the kidney were found to be mis-regulated in the renal cortex and glomeruli of animal models of diabetes as well as in mouse and human mesangial cells treated with TGF-␤ or high glucose, and they could modulate the expression of extracellular matrix genes, suggesting a functional role in DN pathophysiology (3,19,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

“…24,25 The role of miRNAs in kidney diseases has been an area of intense investigation in the past several years. 9,[26][27][28][29][30][31][32] Work from our laboratory and other groups 9,26,[30][31][32] has elucidated the role of numerous miRNAs in the pathophysiology of DN. However, the in vivo functional roles of miRNAs in renal inflammation during DN are not clear.…”

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.…”