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AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Dec 05; Vol. 22 (23). Date of Electronic Publication: 2021 Dec 05. - Publication Year :
- 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 :
- Animals
Aptamers, Nucleotide pharmacology
Cell Movement drug effects
Cell Proliferation drug effects
Disease Models, Animal
Gene Expression Regulation drug effects
Human Umbilical Vein Endothelial Cells
Humans
Intravitreal Injections
Mice
MicroRNAs genetics
Oligodeoxyribonucleotides pharmacology
Phosphoproteins antagonists & inhibitors
Phosphoproteins genetics
Phosphorylation drug effects
RNA-Binding Proteins antagonists & inhibitors
RNA-Binding Proteins genetics
Retinal Neovascularization chemically induced
Retinal Neovascularization genetics
Retinal Neovascularization metabolism
Nucleolin
Aptamers, Nucleotide administration & dosage
Oligodeoxyribonucleotides administration & dosage
Oxygen adverse effects
Phosphoproteins metabolism
RNA-Binding Proteins metabolism
Retinal Neovascularization drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34884955
- Full Text :
- https://doi.org/10.3390/ijms222313150