Endothelial cells (ECs) primarily rely on glycolysis for their energy metabolism, and the final product of glycolysis-lactate-is transferred out of cells via monocarboxylate transporter 4 (MCT4). We previously showed that MCT4 downregulation is involved in diabetic endothelial injury. However, the underlying regulatory mechanisms of MCT4 in diabetes remain unclear. This study showed that miR-425-5p was significantly upregulated in diabetic patients and human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG) and interleukin-1β (IL-1β). MCT4 was shown to be a direct target gene of miR-425-5p, and miR-425-5p expression led to MCT4 downregulation, lactate accumulation and increased apoptosis in HUVECs. Furthermore, the results indicated that NF-κB signaling activation increased miR-425-5p levels and induced MCT4 downregulation, lactate accumulation and apoptosis in HUVECs. In conclusion, NF-κB/miR-425-5p/MCT4 axis activation plays a crucial role in the EC injury induced by HG and IL-1β.
KEYWORDS: Diabetes mellitus, Endothelial dysfunction, Monocarboxylate transporter 4, NF-κB, miR-425-5p