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Title: in vitro angiogenesis miRNA Array      
dateReleased:
09-30-2013
description:
Angiogenesis is a complex multicellular process requiring the orchestration of many events including migration, alignment, proliferation, lumen formation, remodeling, and maturation. Such complexity indicates that not only individual genes but also entire signaling pathways will be crucial in angiogenesis. To define an angiogenic blueprint of regulated genes, we utilized our well-characterized three-dimensional collagen gel model of in vitro angiogenesis, in which the majority of cells synchronously progress through defined morphological stages culminating in the formation of capillary tubes. We developed a comprehensive three-tiered approach using microarray analysis, which allowed us to identify genes known to be involved in angiogenesis and genes hitherto unlinked to angiogenesis as well as novel genes and has proven especially useful for genes where the magnitude of change is small. From a screen of miRNAs altered in in vitro angiogenesis we selected a subset that are predicted to target junctional molecules. MiR-27a, was rapidly downregulated upon stimulation of in vitro angiogenesis and its level of expression is reduced in neo-vessels in vivo. The downregulation of miR-27a was essential for angiogenesis since ectopic expression of miR-27a blocked capillary tube formation and angiogenesis. MiR-27a targets the junctional, endothelial specific cadherin, VE-cadherin. Consistent with this, vascular permeability to VEGF in mice is reduced by administration of a general miR-27 inhibitor. To determine that VE-cadherin was the dominant target of miR-27a function we used a novel technology with “Blockmirs”, inhibitors that bind to the miR-27 binding site in VE-cadherin. The Blockmir CD5-2 demonstrated specificity for VE-cadherin and inhibited vascular leak in vitro and in vivo. Furthermore CD5-2 reduced oedema, increased capillary density and potently enhanced recovery form ischemic limb injury in mice. The Blockmir technology offers a refinement in the use of miRNAs especially for therapy. Further, targeting of endothelial junctional molecules by miRNAs has clinical potential especially in diseases associated with vascular leak. A microRNA microarray was performed to investigate miRNAs that were regulated during capillary tube formation and which could potentially be used as an ‘angiogenic’ miRNA profile. RNA was isolated from cells harvested at specific time points, previously identified as stages where major morphological changes are taking place18. These include 0.5 hour (invasion), 3 hours (migration), 6 hours (vacuole coalescence and lumen formation), 12 hours (lumen formation) and 24 hours (tube maturation).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-50437
refinement:
raw
alternateIdentifiers:
50437
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-17649
name:
Ambion mirVana™ miRNA Probe Set 1564V1
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-50437/E-GEOD-50437.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-50437/E-GEOD-50437.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50437
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress