MiR-181c restrains nitration stress of endothelial cells in diabetic db/db mice through inhibiting the expression of FoxO1

• DOI: 10.1016/j.bbrc.2017.02.083
• Publication Date: 2017-02-21T01:01:18Z
• Authors: Guangwei Yang; Yuanbo Wu; Shandong Ye
• Keywords: Male; Mice, Inbred ICR; 0303 health sciences; Forkhead Box Protein O1; Reverse Transcriptase Polymerase Chain Reaction; Nitrosation; Blotting, Western; Endothelial Cells; Nitric Oxide Synthase Type II; Aorta, Thoracic; Cell Line; Diabetes Mellitus, Experimental; MicroRNAs; 03 medical and health sciences; Glucose; Diabetes Mellitus, Type 2; Gene Expression Regulation; Animals; RNA Interference; Endothelium, Vascular; 3' Untranslated Regions; Cells, Cultured

Endothelial dysfunction played an important role in the progression of diabetes mellitus (DM). miR-181c has been implicated in many diseases, including DM. However, the molecular mechanisms of miR-181c regulate this process remained poorly understood. Healthy ICR mice were divided into control group (n = 10) and db/db DM group (n = 10). The expression of miR-181c and FoxO1 were both investigated in diabetic db/db mice or high glucose-induced endothelial cells (MAECs and END-D). Here we found that down-regulation of miR-181c and the activation of FoxO1/iNOS were observed in mice and endothelial cells. Furthermore, we verified that miR-181c directly targeted and inhibited FoxO1 gene expression by targeting its 3'-UTR through luciferase reporter assay. Knockdown of FoxO1 reversed the up-regulation of iNOS, nitrotyrosine and the down-regulation of p-eNOSSer1177/eNOS in high glucose (30 mM)-induced MAECs cells. In addition, over-expression of miR-181c could reverse the enhanced nitration stress induced by high glucose, while this effect could be attenuated by pcDNA-FoxO1 in MAECs. These results shown that miR-181c attenuated nitration stress through regulating FoxO1 expression and affecting endothelial cell function, which offering a new target for the development of preventive or therapeutic agents against DM.