The NF-κB/miR-425-5p/MCT4 axis: A novel insight into diabetes-induced endothelial dysfunction
The NF-κB/miR-425-5p/MCT4 axis: A novel insight into diabetes-induced endothelial dysfunction
复制标题
NF-kappa B/miR-425-5p/MCT4 轴：对糖尿病引起的内皮功能障碍的新见解
DOI：
10.1016/j.mce.2019.110641
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发表时间：
2020-01-15
影响因子：
4.1
通讯作者：
Tang, Chengchun
中科院分区：
文献类型：
--
作者：
Luo, Erfei;Wang, Dong;Tang, Chengchun
内皮细胞主要依靠糖酵解进行能量代谢，糖酵解的最终产物乳酸通过单羧酸转运蛋白4(MCT4)转移到细胞外。我们先前的研究表明，MCT4下调与糖尿病血管内皮损伤有关。然而，MCT4在糖尿病中的潜在调控机制仍不清楚。本研究表明，在糖尿病患者和经高糖(HG)和白介素1β(IL-1β)处理的人脐静脉内皮细胞(HUVECs)中，miR-425-5p显著上调。MCT4是miR-425-5p的直接靶基因，miR-425-5p的表达导致MCT4表达下调，乳酸蓄积，细胞凋亡率增加。此外，结果表明，核因子-kappa B信号通路的激活增加了人脐静脉内皮细胞miR-425-5p的表达，并诱导了MCT4的下调、乳酸蓄积和细胞凋亡。结论：NF-kappa B/miR-425-5p/MCT4轴激活在HG和IL-1β诱导的内皮细胞损伤中起重要作用。
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-1 beta (IL-1 beta). 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-kappa B signaling activation increased miR-425-5p levels and induced MCT4 downregulation, lactate accumulation and apoptosis in HUVECs. In conclusion, NF-kappa B/miR-425-5p/MCT4 axis activation plays a crucial role in the EC injury induced by HG and IL-1 beta.