Downregulation of microRNA-185 expression in diabetic patients increases the expression of NOS2 and results in vascular injury.

Abstract

The aim of the present study was to investigate the regulatory effect and mechanism of microRNA (miR)-185 in diabetic angiopathy. The expression of miR-185 and nitric oxide synthase 2 (NOS2) in the blood from diabetic patients was examined by reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay. After establishment of diabetic rats, the expression of miR-185 and NOS2 in vascular tissues and blood was also measured. Then, miR-185 was overexpressed in HMEC-1 cells and the expression of NOS2 was determined. Dual-luciferase reporter assay was used to identify the direct interaction between miR-185 and NOS2 mRNA. The expression of NOS2 was upregulated and the expression of miR-185 was downregulated in the blood from patients with diabetes. Vascular tissues and blood of diabetic rats showed similar trends compared with that of human. HMEC-1 cells with overexpression of miR-185 had decreased expression of NOS2. Dual-luciferase reporter assay demonstrated the direct binding between miR-185 and NOS2. The present study demonstrates that upregulation of NOS2 in diabetic patients is associated with the downregulation of miR-185, which participates in the progression of diabetes possibly through regulating NOS2 expression.