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miR‐21‐3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis
Cell Biochemistry and Function ( IF 2.8 ) Pub Date : 2020-03-20 , DOI: 10.1002/cbf.3523
Mingzhe Shao 1 , Muyu Yu 2 , Jun Zhao 1 , Jiacai Mei 1 , Ye Pan 1 , Jian Zhang 1 , Haisheng Wu 1 , Min Yu 2 , Fang Liu 2 , Guangming Chen 3
Affiliation  

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.

中文翻译:

miR-21-3p调节AGE / RAGE信号并改善糖尿病性动脉粥样硬化

探索miR-23-3p对糖尿病动脉粥样硬化的影响。使用酶联免疫吸附测定(ELISA),我们还用具有miR-21-3p模拟物或抑制剂的腺病毒载体转染了血管内皮细胞细胞上清液中的晚期糖基化终产物RAGE(sRAGE)的可溶性受体水平。我们发现高浓度葡萄糖诱导的血管内皮细胞(VEC)中miR-21-3p的表达水平降低。我们还观察到,miR-21-3p模拟物的引入显着增加了VEC中ADAM10的表达。同样,在人静脉内皮细胞中施用miR-21-3p模拟物后,在培养的上清液中发现sRAGE水平显着升高。施用miR-21-3p后,LPS和高浓度葡萄糖诱导的VEC中活性氧的产生和炎性细胞因子的表达显着降低。体内研究表明,定期静脉注射miR-21-3p会减少动脉粥样硬化病变小鼠的面积,并升高血清sRAGE的水平。miR-21-3p可能通过促进sRAGE的裂解形式和抑制RAGE / NADPH氧化酶信号转导而对糖尿病动脉粥样硬化有益,这取决于ADAM10表达的增加。体内研究表明,定期静脉注射miR-21-3p会减少动脉粥样硬化病变小鼠的面积,并升高血清sRAGE的水平。miR-21-3p可能通过促进sRAGE的裂解形式和抑制RAGE / NADPH氧化酶信号转导而对糖尿病动脉粥样硬化有益,这取决于ADAM10表达的增加。体内研究表明,定期静脉注射miR-21-3p会减少动脉粥样硬化病变小鼠的面积,并升高血清sRAGE的水平。miR-21-3p可能通过促进sRAGE的裂解形式和抑制RAGE / NADPH氧化酶信号转导而对糖尿病动脉粥样硬化有益,这取决于ADAM10表达的增加。
更新日期:2020-03-20
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