ZFIN ID: ZDB-PUB-170422-7
Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
Xu, B., Zhang, Y., Du, X.F., Li, J., Zi, H.X., Bu, J.W., Yan, Y., Han, H., Du, J.L.
Date: 2017
Source: Cell Research   27(7): 882-897 (Journal)
Registered Authors: Du, Jiu Lin, Zhang, Yu
Keywords: brain vascular integrity, neuron, endothelial cell, exosome, miR-132, eef2k, zebrafish
Microarrays: GEO:GSE85291
MeSH Terms:
  • Analysis of Variance
  • Animals
  • Antigens, CD/genetics
  • Antigens, CD/metabolism
  • Brain/blood supply*
  • Cadherins/genetics
  • Cadherins/metabolism
  • Elongation Factor 2 Kinase/genetics
  • Elongation Factor 2 Kinase/metabolism
  • Exosomes/genetics
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Intracranial Hemorrhages/metabolism*
  • Intracranial Hemorrhages/pathology
  • Larva
  • Mice
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Neurons
  • Primary Cell Culture
  • Rats
  • Rats, Sprague-Dawley
  • Zebrafish
PubMed: 28429770 Full text @ Cell Res.
FIGURES
ABSTRACT
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.
ADDITIONAL INFORMATION