Volume 27, No 7, Jul 2017
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 27 Issue 7, July 2017: 882-897 | Open Access
ORIGINAL ARTICLES
Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
Bing Xu1,*, Yu Zhang1,2,*, Xu-Fei Du1, Jia Li1, Hua-Xing Zi1,2, Ji-Wen Bu1, Yong Yan1,3, Hua Han4 and Jiu-Lin Du1,2,3
1Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China
2University of Chinese Academy of Sciences, 19A Yu-Quan Road, Beijing 100049, China
3School of Life Science and Technology, ShanghaiTech University, 319 Yue-Yang Road, Shanghai 200031, China
4Institute of Automation, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 95 Zhong-guan-cun East Road, Beijing 100190, China
Correspondence: Jiu-lin Du,(forestdu@ion.ac.cn)
Vascular integrity helps maintain brain microenvironment homeostasis, which is critical for the normal development and function of the central nervous system. It is known that neural cells can regulate brain vascular integrity. However, due to the high complexity of neurovascular interactions involved, understanding of the neural regulation of brain vascular integrity is still rudimentary. Using intact zebrafish larvae and cultured rodent brain cells, we find that neurons transfer miR-132, a highly conserved and neuron-enriched microRNA, via secreting exosomes to endothelial cells (ECs) to maintain brain vascular integrity. Following translocation to ECs through exosome internalization, miR-132 regulates the expression of vascular endothelial cadherin (VE-cadherin), an important adherens junction protein, by directly targeting eukaryotic elongation factor 2 kinase (eef2k). Disruption of neuronal miR-132 expression or exosome secretion, or overexpression of vascular eef2k impairs VE-cadherin expression and brain vascular integrity. Our study indicates that miR-132 acts as an intercellular signal mediating neural regulation of the brain vascular integrity and suggests that the neuronal exosome is a novel avenue for neurovascular communication.
10.1038/cr.2017.62
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