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Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
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Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
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Journal Article
Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
2017
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Brain
/ Elongation Factor 2 Kinase - genetics
/ Elongation Factor 2 Kinase - metabolism
/ Exosomes
/ Human Umbilical Vein Endothelial Cells
/ Humans
/ Intracranial Hemorrhages - metabolism
/ Intracranial Hemorrhages - pathology
/ Kinases
/ Larva
/ Larvae
/ Mice
/ miRNA
/ Neurons
/ Original
/ Rats
/ Rodents
