ABSTRACT
Non-healing lesions in diabetic foot ulcers are a significant effect of poor angiogenesis. Epigenetic regulators, mainly lncRNA and miRNA, are recognized for their important roles in disease progression. We deciphered the regulation of lncRNA NEAT1 through the miR-146a-5p/mafG axis in the progression of DFU. A lowered expression of lncRNA NEAT1 was associated with dysregulated angiogenesis through the reduced expression of mafG, SDF-1α, and VEGF in chronic ulcer subjects compared to acute DFU. This was validated by silencing NEAT1 by SiRNA in the endothelial cells which resulted in the transcriptional repression of target genes. Our in silico analysis identified miR-146a-5p as a potential target of lncRNA NEAT1. Further, silencing NEAT1 led to an increase in the levels of miR-146a-5p in chronic DFU subjects. This research presents the role of the lncRNA NEAT1/miR-146a-5p/mafG axis in enhancing angiogenesis in DFU.
Subject(s)
Diabetic Foot , MicroRNAs , Neovascularization, Physiologic , RNA, Long Noncoding , Humans , Diabetic Foot/pathology , Endothelial Cells/metabolism , MicroRNAs/genetics , RNA, Long Noncoding/geneticsABSTRACT
Chronic hyperglycemia damages the nerves and blood vessels, culminating in other vascular complications. Such complications enhance cytokine, oxidative and endoplasmic reticulum (ER) stress. ER is the primary organelle where proteins are synthesised and attains confirmatory changes before its site of destination. Perturbation of ER homeostasis activates signaling sensors within its lumen, the unfolded protein response (UPR) that orchestrates ER stress and is extensively studied. Increased ER stress markers are reported in diabetic complications in addition to lncRNA that acts as an upstream marker inducing ER stress response. This review focuses on the mechanisms of lncRNA that regulate ER stress markers, especially during the progression of diabetic complications. Through this systemic review, we showcase the dysfunctional lncRNAs that act as a leading cause of ER stress response to the progression of diabetic complications.
