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AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 13150, International Journal of Molecular Sciences, Vol 22, Iss 13150, p 13150 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.
- Subjects :
- nucleolin
AS1411
proliferative retinopathy
HUVEC
oxygen induced retinopathy
aortic rings assay
miR-221 expression levels
QH301-705.5
Retinal Neovascularization
Catalysis
Article
Inorganic Chemistry
Mice
Cell Movement
Human Umbilical Vein Endothelial Cells
Animals
Humans
Biology (General)
Physical and Theoretical Chemistry
Phosphorylation
QD1-999
Molecular Biology
Spectroscopy
Cell Proliferation
Organic Chemistry
RNA-Binding Proteins
General Medicine
Aptamers, Nucleotide
Phosphoproteins
Computer Science Applications
Oxygen
Chemistry
Disease Models, Animal
MicroRNAs
Gene Expression Regulation
Oligodeoxyribonucleotides
Intravitreal Injections
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 22
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....ffacb1a04db78dd6538d4c21eec4a956