Potential Targeting of Renal Fibrosis in Diabetic Kidney Disease Using MicroRNAs

Abstract

Diabetic kidney disease (DKD) is a major health problem and one of the leading causes of end-stage renal disease worldwide. Despite recent advances, there exists an urgent need for the development of new treatments for DKD. DKD is characterized by the excessive synthesis and deposition of extracellular matrix proteins in glomeruli and the tubulointerstitium, ultimately leading to glomerulosclerosis as well as interstitial fibrosis. Renal fibrosis is the final common pathway at the histological level leading to an end-stage renal failure. In fact, activation of the nuclear factor erythroid 2-related factor 2 pathway by bardoxolone methyl and inhibition of transforming growth factor beta signaling by pirfenidone have been assumed to be effective therapeutic targets for DKD, and various basic and clinical studies are currently ongoing. MicroRNAs (miRNAs) are endogenously produced small RNA molecules of 18–22 nucleotides in length, which act as posttranscriptional repressors of gene expression. Studies have demonstrated that several miRNAs contribute to renal fibrosis. In this review, we outline the potential of using miRNAs as an antifibrosis treatment strategy and discuss their clinical application in DKD.

Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis

“…Moreover, podocyte apoptosis is known to be controlled by miR-29c and miR-21, and when miR-29c expression increases, it promotes fibronectin assembly and apoptosis [ 171 ]. The noncoding RNA miR-let-7 decreases ECM protein expression through a mechanism that involves the TGF-β/Smad3 pathway [ 172 ], and DPP-4 inhibition and promotion of peptide AcSDKP expression result in renal protection by regulating crosstalk between miR-29 and miR-let-7 [ 173 ].…”

Human Liver Stem Cell Derived Extracellular Vesicles Alleviate Kidney Fibrosis by Interfering with the β-Catenin Pathway through miR29b

“…miRNAs are single stranded non coding RNA molecules mainly involved in regulating gene expression [ 22 ]. Notably, miRNAs are increasingly demonstrated to act as key regulators of genes involved in the pathophysiology of various diseases, including kidney fibrosis [ 23 , 24 ]. One of the most widely reported miRNA is the miR29 family, which is composed of three extremely similar orthologues (miR29a, miR29b, and miR29c) that share identical seed binding sequences and the ability to bind to similar target genes [ 24 ].…”

Bibliometric Analysis of Renal Fibrosis in Diabetic Kidney Disease From 1985 to 2020

“…Combined with the cluster analysis and the timeline view of references, we could find that microRNAs (miRNAs) are not only the largest clustering but also the emerging research Frontier in recent years. More attention has been paid to miRNAs for their potential fibrotic or antifibrotic effects (29). Researchers found that the dysregulated expression of miRNAs accelerated the ECM accumulation and stimulated pro-fibrotic signaling, finally leading to renal fibrosis (30).…”