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

Abstract

ABSTRACT 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.

Keywords

• Diabetes mellitus
• Hypoxia‐inducible factor
• miR‐31