The NF-κB/miR-425-5p/MCT4 axis: A novel insight into diabetes-induced endothelial dysfunction

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:500

Article

Luo, Erfei¹  Wang, Dong²  Yan, Gaoliang²  Qiao, Yong²  Zhu, Boqian¹  Liu, Bo¹  Hou, Jiantong¹  Tang, Chengchun² 

[1] Southeast Univ, Sch Med, Nanjing 210009, Jiangsu, Peoples R China

[2] Southeast Univ, Zhongda Hosp, Dept Cardiol, Nanjing 210009, Jiangsu, Peoples R China

关键词: NE-kappa B;    miR-425-5p;    Monocarboxylate transporter 4;    Diabetes mellitus;    Endothelial dysfunction;   

DOI  :  10.1016/j.mce.2019.110641

来源: Elsevier

【 摘 要 】

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.

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