The function of miRNAs in the process of kidney development

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that typically consist of 19-25 nucleotides in length. These molecules function as essential regulators of gene expression by selectively binding to complementary target sequences within messenger RNA (mRNA) molecules, consequently exerting a negative impact on gene expression at the post-transcriptional level. By modulating the stability and translation efficiency of target mRNAs, miRNAs play pivotal roles in diverse biological processes, including the intricate orchestration of organ development. Among these processes, the development of the kidney has emerged as a key area of interest regarding miRNA function. Intriguingly, recent investigations have uncovered a subset of miRNAs that exhibit remarkably high expression levels in the kidney, signifying their close association with kidney development and diseases affecting this vital organ. This growing body of evidence strongly suggests that miRNAs serve as crucial regulators, actively shaping both the physiological processes governing kidney function and the pathological events leading to renal disorders. This comprehensive review aims to provide an up-to-date overview of the latest research progress regarding miRNAs and their involvement in kidney development. By examining the intricate interplay between miRNAs and the molecular pathways driving kidney development, this review seeks to elucidate the underlying mechanisms through which miRNAs exert their regulatory functions. Furthermore, an in-depth exploration of the role played by miRNAs in the occurrence and progression of renal dysplasia will be presented. Renal dysplasia represents a significant developmental anomaly characterized by abnormal kidney tissue formation, and miRNAs have emerged as key players in this pathological process. By shedding light on the intricate network of miRNA-mediated regulatory mechanisms involved in kidney dysplasia, this review aims to provide valuable insights for the diagnosis and research of diseases associated with aberrant kidney development.

Keywords: Kidney development; Kidney dysplasia; Mechanism; Pathology; lncRNAs; miRNAs.

Fig. 1

Illustrates the process of microRNA (miRNA) formation and its functional role. (A) MiRNAs are generally classified as intronic or intergenic based upon their genomic location. (B) The miRNA gene is transcribed by RNA polymerase II (RNA Pol II) into a primary miRNA (pri-miRNA) transcript. The Microprocessor complex (DGCR8-Drosha) processes the pri-miRNA into a precursor miRNA (pre-miRNA), which is then exported to the cytoplasm through the transport protein exportin-5 (XPO5). In the cytoplasm, the pre-miRNA is cleaved by Dicer, generating the mature miRNA. The mature miRNA recognizes its target mRNA, recruits the RNA-induced silencing complex (RISC), and mediates post-transcriptional inhibition of the target by translation repression, adenylation, and/or enhanced mRNA degradation.

Fig. 2

Assigning the congenital anomalies of the kidney and urinary tract (CAKUT)-related biological functions to some microRNAs (miRNAs). Among CAKUT categories, congenital obstructive uropathy represents a common and severe form of malformation. Transforming growth factor beta (TGF-b) and tumor necrosis factor alpha (TNF-α) are well known as central mediators of fibrosis and inflammation and are thought to play an important role in the progression of CAKUT. The increase of monocyte chemoattractant protein-1 (MCP-1) expression levels suggests that the main factor responsible for the above effects is chronic renal inflammation mediated by local monocytes. MiRNAs play an important role in the regulation of these target genes and downstream signaling pathways (RANTES, mouse double minute 2 homolog (MDM2), apoptotic protease activating factor 1 (APAF1), NOTCH3, and extracellular matrix (ECM)-receptor interaction signaling pathways).