miR‐21‐3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis

Abstract

To explore the effects of miR-21-3p on diabetic atherosclerosis. Using enzyme-linked immunosorbent assay (ELISA), we also detected the levels of soluble receptor for advanced glycation endproducts RAGE (sRAGE) in the cellular supernatant of vascular endothelial cells after transfecting them with adenovirus vector having miR-21-3p mimic or inhibitor. We found decrease in the expression levels of miR-21-3p in vascular endothelial cells (VECs) induced by high-concentration glucose. We also observed that the introduction of miR-21-3p mimic significantly increased the expression of ADAM10 in the VECs. Similarly, significantly higher levels of sRAGE were found in the cultured supernatant after administration of miR-21-3p mimic in human vein endothelial cells. The production of reactive oxygen species and expression of inflammatory cytokines in VECs induced by LPS and high-concentration glucose were significantly decreased after administration of miR-21-3p. in vivo studies revealed that intravenous injection of miR-21-3p at regular intervals would reduce the area of atherosclerotic lesion and elevate the serum levels of sRAGE in atherosclerotic diabetic mice. miR-21-3p may be beneficial in diabetic atherosclerosis by promoting the cleaved form of sRAGE and inhibition of RAGE/NADPH oxidase signalling depending on the increased expression of ADAM10. Significance of the Study: We identified a novel microRNA, miR-21-3p, which is characteristically at elevated levels in serum derived from diabetic patients and responsible for target degradation of ADAM10 mRNA. Further, we show that miR-21-3p aggravates the atherosclerotic lesion via dysfunction of the ectodomain shedding of molecular binding RAGE in the diabetic atherosclerotic mice.

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

“…Exposure of cultured vascular endothelial cells to diabetesrelevant concentrations of glucose was found to decrease the expression levels of miR-21-3p and the introduction of miR-21-3p mimic significantly increased the expression of A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in these cells and, ac-cordingly, in the presence of the miR-21-3p mimic, the concentrations of sRAGE were found to increase in these cells. In vivo, intravenous injections of miR-21-3p reduced diabetic atherosclerosis and increased serum levels of sRAGE in mice models, thereby implicating this miR in the regulation of RAGE ectodomain shedding [55]. These findings provide further insights into the mechanisms by which soluble RAGE (cleaved) may be produced in vivo and, thereby, highlight new therapeutic opportunities for diabetic atherosclerosis.…”

Prognostic value of pulmonary ultrasound score combined with plasma miR‐21‐3p expression in patients with acute lung injury

“…It was reported that miR‐21‐3p regulates AGE/RAGE signaling and improves diabetic atherosclerosis. 16 There is a significant increase in the serum level of miR‐21‐3p in children with sepsis‐induced acute kidney injury, 17 and miR‐21‐3p promotes hepatocellular carcinoma progression via SMAD7/YAP1 regulation. 18 In addition, miR‐21‐3p can regulate the prognosis of gastric cancer and colorectal cancer.…”

MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4

“…microRNAs play a crucial regulatory role in the progression of various diseases ( 28 – 31 ). A study found that miR-21-3p is involved in the onset and progression of SIC ( 32 ). The miR-144-3p/NF-kB signaling pathway can regulate SIC injury ( 33 ).…”