The Role of miRNA in Renal Fibrosis Leading to Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is an important health concern that is expected to be the fifth most widespread cause of death worldwide by 2040. The presence of chronic inflammation, oxidative stress, ischemia, etc., stimulates the development and progression of CKD. Tubulointerstitial fibrosis is a common pathomechanism of renal dysfunction, irrespective of the primary origin of renal injury. With time, fibrosis leads to end-stage renal disease (ESRD). Many studies have demonstrated that microRNAs (miRNAs, miRs) are involved in the onset and development of fibrosis and CKD. miRNAs are vital regulators of some pathophysiological processes; therefore, their utility as therapeutic agents in various diseases has been suggested. Several miRNAs were demonstrated to participate in the development and progression of kidney disease. Since renal fibrosis is an important problem in chronic kidney disease, many scientists have focused on the determination of miRNAs associated with kidney fibrosis. In this review, we present the role of several miRNAs in renal fibrosis and the potential pathways involved. However, as well as those mentioned above, other miRs have also been suggested to play a role in this process in CKD. The reports concerning the impact of some miRNAs on fibrosis are conflicting, probably because the expression and regulation of miRNAs occur in a tissue- and even cell-dependent manner. Moreover, different assessment modes and populations have been used. There is a need for large studies and clinical trials to confirm the role of miRs in a clinical setting. miRNAs have great potential; thus, their analysis may improve diagnostic and therapeutic strategies.

Keywords: chronic kidney disease; fibrosis; miRNA.

Figure 1

The mechanisms observed during renal fibrosis. ↑ increased; ↓ reduced; CCL5, C-C motif chemokine ligand 5; ECM, extracellular matrix; EMT, epithelial–mesenchymal transition; FGF-2, fibroblast growth factor 2; MCP1, monocyte chemoattractant protein-1; MMP2- matrix metalloproteinase 2; MMP9- matrix metalloproteinase 9; PAI1, plasminogen activator inhibitor-1; PDGF, platelet-derived growth factor; ROS, reactive oxygen species; TGF-β1, transforming growth factor β1.