The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress

Abstract

Diabetic nephropathy (DN) is one of the main complications of diabetes and the main cause of diabetic end-stage renal disease, which is often fatal. DN is usually characterized by progressive renal interstitial fibrosis, which is closely related to the excessive accumulation of extracellular matrix and oxidative stress. Non-coding RNAs (ncRNAs) are RNA molecules expressed in eukaryotic cells that are not translated into proteins. They are widely involved in the regulation of biological processes, such as, chromatin remodeling, transcription, post-transcriptional modification, and signal transduction. Recent studies have shown that ncRNAs play an important role in the occurrence and development of DN and participate in the regulation of oxidative stress in DN. This review clarifies the functions and mechanisms of ncRNAs in DN-related oxidative stress, providing valuable insights into the prevention, early diagnosis, and molecular therapeutic targets of DN.

Keywords: diabetic nephropathy; mircoRNA; ncRNA; oxidative stress; therapeutic target.

Figure 1

The regulatory mechanism of ncRNAs. (A) miRNA can direct bind with the 3′ UTR of the target gene. (B) LncRNA serves as ceRNA to interact with miRNAs. (C) LncRNA acts as a scaffold via recruiting and interacting with proteins and regulate the activity of proteins. (D) LncRNA acts as a guide to promote the gene expression via recruiting transcription factors (TF) to the region of the gene promoter. (E) LncRNA acts as a decoy via interacting with TF to inhibit transcriptional regulation. (F) CircRNA serves as ceRNA to interact with miRNAs. (G) CircRNA acts as a scaffold via recruiting and interacting with proteins and regulate the activity of proteins.

Figure 2

Schematic demonstration of the crosstalks between DN and signaling pathways.

Figure 3

The relationship between ncRNAs and DN-associated oxidative stress. HG, high glucose; AR, aldose reductase; CASC2, cancer susceptibility candidate 2; HMGB1, high mobility group box 1; SOD, superoxide dismutase; NOX4, nicotinamide adenine dinucleotide phosphate oxidase 4; FN, fibronectin; TGF-β1:transforming growth factor β1:TXNRD2, thioredoxin reductase 2; FOXP1, forkhead box P1; NRF2, nuclear factor erythroid E2-related factor 2; SEMA3A, semaphorin 3A; Foxo1, Forkhead box 1; ROS, reactive oxygen species; AKT, protein kinase B; mTOR, mechanistic target of rapamycin; UCP2, uncoupling protein 2; SIRT1, Sirtuin 1; NF-κB, nuclear factor-kappa B; PTEN, phosphatase and tensin homolog; PHD1, prolyl hydroxylase 1.