Abstract
Large-scale RNA sequencing and genome-wide profiling data revealed the identification of a heterogeneous group of noncoding RNAs, known as long noncoding RNAs (lncRNAs). These lncRNAs play central roles in health and disease processes in diabetes and cancer. The critical association between aberrant expression of lncRNAs in diabetes and diabetic kidney disease have been reported. LncRNAs regulate diverse targets and can function as sponges for regulatory microRNAs, which influence disease phenotype in the kidneys. Importantly, lncRNAs and microRNAs may regulate bidirectional or crosstalk mechanisms, which need to be further investigated. These studies offer the novel possibility that lncRNAs may be used as potential therapeutic targets for diabetes and diabetic kidney diseases. Here, we discuss the functions and mechanisms of actions of lncRNAs, and their crosstalk interactions with microRNAs, which provide insight and promise as therapeutic targets, emphasizing their role in the pathogenesis of diabetes and diabetic kidney disease
Highlights
Available evidence has indicated the important roles of long noncoding RNAs (lncRNAs) in the pathophysiology of diabetic kidney disease (DKD), and the crosstalk between lncRNAs and DKD
In the kidneys of COL4A3 knockout mice, 45% of all αSMA-positive fibroblasts and 60% of all Fibroblast-specific protein 1 (FSP-1)-positive fibroblasts were CD31-positive, suggesting that these fibroblasts are of endothelial origin and that endothelial-to-mesenchymal transitions (EndMT) might contribute critically to the development and progression of renal fibrosis [74]
Long non-coding RNAs (LncRNAs) H19 is associated with kidney fibrosis by activating EndMT processes in diabetes (Figure 1)
Summary
Gene expression profiling and in situ hybridization studies have shown that the expression of lncRNAs can be tissue- and cell-specific, and may vary spatially, temporally or in response to stimuli [5]. LncRNAs are classified into four groups based on their location in the genome: (1) the intergenic lncRNAs, (2) the sense or antisense lncRNAs, (3) the intronic lncRNAs and (4) the processed transcripts; these lncRNAs reside in a gene-loci that has no ORF [6,7] Based on their functions, lncRNAs have been characterized as signal, decoy, scaffold, guide, enhancer RNAs and short peptides [8,9]. Decoy lncRNAs act by reducing the availability of key molecules that are involved in gene regulation. These lncRNAs alter the transcription level by sequestering regulatory factors, and microRNAs, minimizing their expression level [11]. Guide lncRNAs interact with ribonucleoproteins complex and influence the gene transcriptional level [14]
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