2. Academic Validation
  3. 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

  • Mol Cell Endocrinol. 2020 Jan 15;500:110641. doi: 10.1016/j.mce.2019.110641.
Erfei Luo 1,  Dong Wang 2,  Gaoliang Yan 3,  Yong Qiao 4,  Boqian Zhu 5,  Bo Liu 6,  Jiantong Hou 7,  Chengchun Tang 8
Affiliations

Affiliations

  • 1 School of Medicine, Southeast University, Nanjing, 210009, China. Electronic address: luoerfeiseu@163.com.
  • 2 Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, 210009, China. Electronic address: wangdong_seu@163.com.
  • 3 Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, 210009, China. Electronic address: yanshipingguo@163.com.
  • 4 Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, 210009, China. Electronic address: jingyong8866@163.com.
  • 5 School of Medicine, Southeast University, Nanjing, 210009, China. Electronic address: zhuboqian0610@163.com.
  • 6 School of Medicine, Southeast University, Nanjing, 210009, China. Electronic address: southeast5865@126.com.
  • 7 School of Medicine, Southeast University, Nanjing, 210009, China. Electronic address: bigbang89757@126.com.
  • 8 Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, 210009, China. Electronic address: tangchengchun@hotmail.com.
PMID: 31711985 DOI: 10.1016/j.mce.2019.110641
Abstract

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.

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