miR-31通过上调缺氧诱导因子-1α/血管内皮生长因子- a改善2型糖尿病血管损伤

IF 3.2 3区 医学
Yuan Fu, Ruochen Du, Yufei Wang, Yitong Yuan, Yujuan Zhang, Chunfang Wang, Xuanping Zhang
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引用次数: 1

摘要

目的:微rna可能是糖尿病治疗的新方向。miR-31作为一种典型的肿瘤标志物,参与多种代谢性疾病,但具体作用尚不清楚。本研究旨在探讨miR-31对2型糖尿病及其伴随血管损伤的影响,以及在体外和体内对缺氧诱导因子-1α抑制剂(HIF1AN)、缺氧诱导因子(HIF)-1α、血管内皮生长因子(VEGF)-A表达的影响。材料与方法体外建立高脂高糖诱导的人主动脉内皮细胞(HAEC)损伤模型,模拟糖尿病(DM)。比较对照组、DM损伤组和DM损伤后转染miR-31组的细胞功能。在体内,将过表达miR-31的FVB小鼠和FVB小鼠分为对照组和诱导型2型糖尿病组。采用高脂饮食联合链脲佐菌素诱导2型糖尿病模型。比较对照组和2型糖尿病组的脂质代谢水平、脏器和血管损伤情况。结果在体外,miR-31通过靶向HIF1AN,上调HIF-1α和VEGF-A的表达,提高受损细胞的增殖能力。在体内,miR-31改善了2型糖尿病的发展、糖脂代谢紊乱以及一些器官的损伤。同时,miR-31通过提高HIF-1α和VEGF-A水平对2型糖尿病并发血管损伤具有保护作用。结论miR-31可以延缓2型糖尿病的进展,改善糖尿病血管损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

miR-31 ameliorates type 2 diabetic vascular damage through up-regulation of hypoxia-inducible factor-1α/vascular endothelial growth factor-A

miR-31 ameliorates type 2 diabetic vascular damage through up-regulation of hypoxia-inducible factor-1α/vascular endothelial growth factor-A

Aims

microRNA may be a new therapeutic direction for diabetes. As a typical tumor marker, miR-31 is involved in a variety of metabolic diseases, but the specific role is still unclear. This study aimed to investigate the effect of miR-31 on type 2 diabetes mellitus and its accompanying vascular injury, as well as on the effects of hypoxia-inducible factor-1α inhibitor (HIF1AN), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF)-A expression in vitro and in vivo.

Materials and Methods

In vitro, a model of high-fat and high-glucose-induced human aortic endothelial cell (HAEC) injury was established to simulate diabetes mellitus (DM). Cell functions were compared between the control group, the DM damage group, and the group transfected with miR-31 after DM damage. In vivo, overexpressing miR-31 FVB mice and FVB mice were divided into the control and induced type 2 diabetes mellitus groups. Type 2 diabetes mellitus models were induced by a high-fat diet combined with streptozotocin. The lipid metabolism levels, viscera, and vascular damage were compared between the control and type 2 diabetes mellitus groups.

Results

In vitro, miR-31 improved the proliferation ability of damaged cells by targeting HIF1AN and up-regulating the expression of HIF-1α and VEGF-A. In vivo, miR-31 ameliorated the development of type 2 diabetes mellitus, disturbance of glucose and lipid metabolism, and damage to some organs. Meanwhile, miR-31 had a protective effect on vascular damage complicated by type 2 diabetes mellitus by increasing the levels of HIF-1α and VEGF-A.

Conclusion

Our experiments show that miR-31 can delay the progression of type 2 diabetes mellitus and ameliorate diabetic vascular injury.

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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation Medicine-Internal Medicine
自引率
9.40%
发文量
218
期刊介绍: Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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