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Volume 22
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10.3390/ijms222313150
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Article

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation

by
Emilio Iturriaga-Goyon
1,2,
Oscar Vivanco-Rojas
2,
Fátima Sofía Magaña-Guerrero
2,
Beatriz Buentello-Volante
2,
Ilse Castro-Salas
2,
José Eduardo Aguayo-Flores
2,
Isabel Gracia-Mora
3,
Marisol Rivera-Huerta
3,
Francisco Sánchez-Bartés
3 and
Yonathan Garfias
2,4,*
1
MD/Ph.D. (PECEM) Program, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, Mexico
2
Research Unit, Institute of Ophthalmology, Conde de Valenciana, Chimalpopoca 14, Ciudad de Mexico 06800, Mexico
3
Unidad de Experimentación Preclínica, Department of Inorganic and Nuclear Chemistry, Faculty of Chemistry, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Ciudad de Mexico 04510, Mexico
4
Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Ciudad de Mexico 04510, Mexico
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(23), 13150; https://doi.org/10.3390/ijms222313150
Submission received: 30 October 2021 / Revised: 26 November 2021 / Accepted: 2 December 2021 / Published: 5 December 2021
(This article belongs to the Special Issue Advances in Molecular Activity of Potential Drugs)
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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.
Keywords: nucleolin; AS1411; proliferative retinopathy; HUVEC; oxygen induced retinopathy; aortic rings assay; miR-221 expression levels nucleolin; AS1411; proliferative retinopathy; HUVEC; oxygen induced retinopathy; aortic rings assay; miR-221 expression levels

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MDPI and ACS Style

Iturriaga-Goyon, E.; Vivanco-Rojas, O.; Magaña-Guerrero, F.S.; Buentello-Volante, B.; Castro-Salas, I.; Aguayo-Flores, J.E.; Gracia-Mora, I.; Rivera-Huerta, M.; Sánchez-Bartés, F.; Garfias, Y. AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation. Int. J. Mol. Sci. 2021, 22, 13150. https://doi.org/10.3390/ijms222313150

AMA Style

Iturriaga-Goyon E, Vivanco-Rojas O, Magaña-Guerrero FS, Buentello-Volante B, Castro-Salas I, Aguayo-Flores JE, Gracia-Mora I, Rivera-Huerta M, Sánchez-Bartés F, Garfias Y. AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation. International Journal of Molecular Sciences. 2021; 22(23):13150. https://doi.org/10.3390/ijms222313150

Chicago/Turabian Style

Iturriaga-Goyon, Emilio, Oscar Vivanco-Rojas, Fátima Sofía Magaña-Guerrero, Beatriz Buentello-Volante, Ilse Castro-Salas, José Eduardo Aguayo-Flores, Isabel Gracia-Mora, Marisol Rivera-Huerta, Francisco Sánchez-Bartés, and Yonathan Garfias. 2021. "AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation" International Journal of Molecular Sciences 22, no. 23: 13150. https://doi.org/10.3390/ijms222313150

APA Style

Iturriaga-Goyon, E., Vivanco-Rojas, O., Magaña-Guerrero, F. S., Buentello-Volante, B., Castro-Salas, I., Aguayo-Flores, J. E., Gracia-Mora, I., Rivera-Huerta, M., Sánchez-Bartés, F., & Garfias, Y. (2021). AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation. International Journal of Molecular Sciences, 22(23), 13150. https://doi.org/10.3390/ijms222313150

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