MicroRNA-106 attenuates hyperglycemia-induced vascular endothelial cell dysfunction by targeting HMGB1

Abstract

Chronic wounds are a common surgical problem exacerbated by diabetes. A hyperglycemic microenvironment induces inflammation and apoptosis, and plays an important role in vascular endothelial cell dysfunction in diabetes. Increasing evidence shows that high mobility group box 1 (HMGB1) expression is related to inflammation and apoptosis. The aim of this study was to determine the function of HMGB1 in hyperglycemia-induced vascular endothelial cell dysfunction. The results showed that the expression of HMGB1 was increased in human umbilical vein endothelial cells (HUVECs) after exposure to high glucose (25 mM). Downregulation of HMGB1 attenuated the high glucose-induced antiangiogenesis of HUVECs, and the decrease expression of HMGB1 inhibiting HUVEC apoptosis and inflammatory factor expression. In addition, miR-106 expression in HUVECs was decreased under high glucose conditions. Increased miR-106 significantly reversed the high glucose-induced vascular endothelial cell dysfunction by inhibition of HUVEC apoptosis and inflammatory factor expression. However, HMGB1 overexpression attenuated the protective effect of miR-106 on HUVECs in high glucose conditions. This suggested that miR-106 suppressed hyperglycemia-induced vascular endothelial cell dysfunction by targeting HMGB1. Double fluorescent reporter assays confirmed that miR-106 interacted with the 3'-UTR of HMGB1 and inhibited HMGB1 expression. Taken together, these data collectively suggested that miR-106 was a potential molecular target for inhibiting high glucose-induced inflammation and apoptosis by targeting HMGB1.

Keywords: Apoptosis; HMGB1; Hyperglycemia; Inflammation; MiR-106.