Dilara Z. Gatina
Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors
Gatina, Dilara Z.; Garanina, Ekaterina E.; Zhuravleva, Margarita N.; Synbulatova, Gulnaz E.; Mullakhmetova, Adelya F.; Solovyeva, Valeriya V.; Kiyasov, Andrey P.; Rutland, Catrin S.; Rizvanov, Albert A.; Salafutdinov, Ilnur I.
Authors
Ekaterina E. Garanina
Margarita N. Zhuravleva
Gulnaz E. Synbulatova
Adelya F. Mullakhmetova
Valeriya V. Solovyeva
Andrey P. Kiyasov
CATRIN RUTLAND CATRIN.RUTLAND@NOTTINGHAM.AC.UK
Associate Professor
Albert A. Rizvanov
Ilnur I. Salafutdinov
Abstract
Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses’ furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases.
Citation
Gatina, D. Z., Garanina, E. E., Zhuravleva, M. N., Synbulatova, G. E., Mullakhmetova, A. F., Solovyeva, V. V., …Salafutdinov, I. I. (2021). Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors. International Journal of Molecular Sciences, 22(11), Article 5922. https://doi.org/10.3390/ijms22115922
Journal Article Type | Article |
---|---|
Acceptance Date | May 27, 2021 |
Online Publication Date | May 31, 2021 |
Publication Date | Jun 1, 2021 |
Deposit Date | Jun 2, 2021 |
Publicly Available Date | Jun 2, 2021 |
Journal | International Journal of Molecular Sciences |
Print ISSN | 1661-6596 |
Publisher | MDPI AG |
Peer Reviewed | Peer Reviewed |
Volume | 22 |
Issue | 11 |
Article Number | 5922 |
DOI | https://doi.org/10.3390/ijms22115922 |
Keywords | Physical and Theoretical Chemistry; Inorganic Chemistry; Organic Chemistry; Spectroscopy; Molecular Biology; Catalysis; General Medicine; Computer Science Applications |
Public URL | https://nottingham-repository.worktribe.com/output/5622649 |
Publisher URL | https://www.mdpi.com/1422-0067/22/11/5922 |
Files
Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors
(23.8 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
You might also like
The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer
(2022)
Journal Article
Anatomy, histology, development and functions of Ossa cordis: A review
(2022)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: digital-library-support@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search