RRC ID 51279
Author Xu B, Zhang Y, Du XF, Li J, Zi HX, Bu JW, Yan Y, Han H, Du JL.
Title Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity.
Journal Cell Res
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.
Volume 27(7)
Pages 882-897
Published 2017-7-1
DOI 10.1038/cr.2017.62
PII cr201762
PMID 28429770
PMC PMC5518987
MeSH 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 Exosomes / metabolism* Human Umbilical Vein Endothelial Cells Humans Intracranial Hemorrhages / metabolism* Intracranial Hemorrhages / pathology Larva Mice MicroRNAs / genetics MicroRNAs / metabolism* Neurons / metabolism* Primary Cell Culture Rats Rats, Sprague-Dawley Zebrafish
IF 20.507
Times Cited 68
Zebrafish Tg(HuC:cameleon2.1)