周细胞
生物
血脑屏障
内皮
过剩1
血管生成
糖酵解
内皮干细胞
细胞生物学
葡萄糖转运蛋白
血管通透性
一元羧酸盐转运体
内科学
内分泌学
生物化学
新陈代谢
运输机
癌症研究
体外
中枢神经系统
基因
胰岛素
医学
作者
H. Lee,Yanying Xu,Xiaolong Zhu,Cholsoon Jang,Woosung Choi,Hosung Bae,Weiwei Wang,Liqun He,S. Jin,Zoltan Arany,Michael Simons
标识
DOI:10.15252/embj.2021109890
摘要
Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial-pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes. Inhibition of lactate production in the endothelium by deletion of the glucose transporter-1 (GLUT1) in mice results in loss of pericyte coverage in the retina and brain vasculatures, leading to the blood-brain barrier breakdown and increased permeability. These abnormalities can be largely restored by oral lactate administration. Our studies demonstrate an unexpected link between endothelial and pericyte metabolisms and the role of endothelial lactate production in the maintenance of the blood-brain barrier integrity. In addition, our observations indicate that lactate supplementation could be a useful therapeutic approach for GLUT1 deficiency metabolic syndrome patients.
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