Angiogenesis and nerve regeneration induced by local administration of plasmid pBud-coVEGF165-coFGF2 into the intact rat sciatic nerve
| Autor: | A. A. Bogov, Adilet Abdullaatovich Kadyrov, Alina Zeinalova, Ilnur I. Salafutdinov, D. Andreeva, Valeriia Syromiatnikova, Ruslan Masgutov, Adelya Mullakhmetova, Kamilla Idrisova, Liliya Mukhametova, Galina Masgutova, Igor O. Pankov, Albert A. Rizvanov, Ekaterina E. Garanina |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
business.industry Angiogenesis Pharmacology Fibroblast growth factor lcsh:RC346-429 Vascular endothelial growth factor 03 medical and health sciences chemistry.chemical_compound Vascular endothelial growth factor A 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure chemokines cytokines fibroblast growth factor gene therapy growth factors peripheral nerve system sciatic nerve regeneration vascular endothelial growth factor Developmental Neuroscience chemistry Epidermal growth factor Epineurium Medicine Tumor necrosis factor alpha Sciatic nerve business 030217 neurology & neurosurgery lcsh:Neurology. Diseases of the nervous system |
| Zdroj: | Neural Regeneration Research, Vol 16, Iss 9, Pp 1882-1889 (2021) |
| ISSN: | 1673-5374 |
| Popis: | Vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) are well-known growth factors involved in the regeneration of various tissues and organs, including peripheral nerve system. In the present study, we elucidated the local and systemic effects of plasmid construct рBud-coVEGF165-coFGF2 injected into the epineurium of intact rat sciatic nerve. Results of histological examination of sciatic nerve and multiplex immunoassays of serum showed the absence of immunogenicity and biosafety of plasmid рBud-coVEGF165-coFGF2. Moreover, local administration of plasmid DNA construct resulted in significantly decreased levels of pro-inflammatory cytokines in the peripheral blood, including tumor necrosis factor α (TNFα) and interleukin-12, and significantly increased levels of cytokines and chemokines including Regulated upon Activation, Normal T Cell Expressed and Presumably Secrete (RANTES), epidermal growth factor, interleukin-2, and monocyte chemoattractant protein 1. These changes in the peripheral blood on day 7 after injection of plasmid construct рBud-coVEGF165-coFGF2 show that the plasmid construct has systemic effects and may modulate immune response. At the same time, reverse transcription-polymerase chain reaction revealed transient expression of coFGF2, coVEGF165, ratFGF2 and ratVEGFA with direct transport of transcripts from distal part to proximal part of the sciatic nerve. Immunohistochemical staining revealed prolonged presence of VEGFA in sciatic nerve till 14 days post-injection. These findings suggest that local administration of plasmid construct рBud-coVEGF165-coFGF2 at a concentration of 30 ng/µL results in the formation of pro-angiogenic stimuli and, and the plasmid construct, used as a drug for gene therapy, might potentially facilitate regeneration of the sciatic nerve. The study was approved by the Animal Ethics Committee of Kazan Federal University, procedures were approved by the Local Ethics Committee (approval No. 5) on May 27, 2014. |
| Databáze: | OpenAIRE |
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