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.

中文翻译：

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NF-κB/ miR-425-5p / MCT4轴：糖尿病引起的内皮功能异常的新见解。

内皮细胞（EC）主要依靠糖酵解来进行能量代谢，糖酵解的最终产物乳酸盐通过单羧酸盐转运蛋白4（MCT4）从细胞中转移出来。我们先前显示，MCT4下调与糖尿病内皮损伤有关。但是，MCT4在糖尿病中的潜在调控机制仍不清楚。这项研究表明，在接受高糖（HG）和白介素-1β（IL-1β）治疗的糖尿病患者和人脐静脉内皮细胞（HUVEC）中，miR-425-5p明显上调。MCT4被证明是miR-425-5p的直接靶基因，miR-425-5p的表达导致HUVEC中MCT4的下调，乳酸盐的积累和细胞凋亡的增加。此外，结果表明NF-κB信号激活增加了miR-425-5p的水平并诱导了MCT4的下调，HUVEC中乳酸的积累和凋亡。总之，NF-κB/ miR-425-5p / MCT4轴激活在HG和IL-1β诱导的EC损伤中起关键作用。