An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury
Spinal cord injury (SCI) leads to local vascular disruption and progressive ischemia, which contribute to secondary degeneration. Enhancing angiogenesis through the induction of vascular endothelial growth factor (VEGF)-A expression therefore constitutes an attractive therapeutic approach. Moreover,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109003040 |
| _version_ | 1818560463609266176 |
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| author | Yang Liu Sarah Figley S. Kaye Spratt Gary Lee Dale Ando Richard Surosky Michael G. Fehlings |
| author_facet | Yang Liu Sarah Figley S. Kaye Spratt Gary Lee Dale Ando Richard Surosky Michael G. Fehlings |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | Spinal cord injury (SCI) leads to local vascular disruption and progressive ischemia, which contribute to secondary degeneration. Enhancing angiogenesis through the induction of vascular endothelial growth factor (VEGF)-A expression therefore constitutes an attractive therapeutic approach. Moreover, emerging evidence suggests that VEGF-A may also exhibit neurotrophic, neuroprotective, and neuroproliferative effects. Building on this previous work, we seek to examine the potential therapeutic benefits of an engineered zinc finger protein (ZFP) transcription factor designed to activate expression of all isoforms of endogenous VEGF-A (ZFP-VEGF). Administration of ZFP-VEGF resulted in increased VEGF-A mRNA and protein levels, an attenuation of axonal degradation, a significant increase in vascularity and decreased levels of apoptosis. Furthermore, ZFP-VEGF treated animals showed significant improvements in tissue preservation and neurobehavioural outcomes. These data suggest that activation of VEGF-A via the administration of an engineered ZFP transcription factor holds promise as a therapy for SCI and potentially other forms of neurotrauma. |
| first_indexed | 2024-12-14T00:38:45Z |
| format | Article |
| id | doaj.art-874e75f71bc2451b9a566baa4ae23a11 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T00:38:45Z |
| publishDate | 2010-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-874e75f71bc2451b9a566baa4ae23a112022-12-21T23:24:30ZengElsevierNeurobiology of Disease1095-953X2010-02-01372384393An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injuryYang Liu0Sarah Figley1S. Kaye Spratt2Gary Lee3Dale Ando4Richard Surosky5Michael G. Fehlings6Department of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, CanadaDepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Ontario, CanadaDepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, CA, USADepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, CA, USADepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, CA, USADepartment of Therapeutic Development, Sangamo BioSciences, Pt. Richmond, CA, USADepartment of Genetics and Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Ontario, Canada; Corresponding author. Division of Neurosurgery, and Division of Genetics and Development, University Health Network, University of Toronto, 399 Bathurst St. 4WW-449, Toronto, ON, Canada M5T 2S8. Fax: +1 416 603 5745.Spinal cord injury (SCI) leads to local vascular disruption and progressive ischemia, which contribute to secondary degeneration. Enhancing angiogenesis through the induction of vascular endothelial growth factor (VEGF)-A expression therefore constitutes an attractive therapeutic approach. Moreover, emerging evidence suggests that VEGF-A may also exhibit neurotrophic, neuroprotective, and neuroproliferative effects. Building on this previous work, we seek to examine the potential therapeutic benefits of an engineered zinc finger protein (ZFP) transcription factor designed to activate expression of all isoforms of endogenous VEGF-A (ZFP-VEGF). Administration of ZFP-VEGF resulted in increased VEGF-A mRNA and protein levels, an attenuation of axonal degradation, a significant increase in vascularity and decreased levels of apoptosis. Furthermore, ZFP-VEGF treated animals showed significant improvements in tissue preservation and neurobehavioural outcomes. These data suggest that activation of VEGF-A via the administration of an engineered ZFP transcription factor holds promise as a therapy for SCI and potentially other forms of neurotrauma.http://www.sciencedirect.com/science/article/pii/S0969996109003040SCIZFP-VEGFAngiogenesisNeuroprotectionMolecular therapy |
| spellingShingle | Yang Liu Sarah Figley S. Kaye Spratt Gary Lee Dale Ando Richard Surosky Michael G. Fehlings An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury Neurobiology of Disease SCI ZFP-VEGF Angiogenesis Neuroprotection Molecular therapy |
| title | An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury |
| title_full | An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury |
| title_fullStr | An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury |
| title_full_unstemmed | An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury |
| title_short | An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury |
| title_sort | engineered transcription factor which activates vegf a enhances recovery after spinal cord injury |
| topic | SCI ZFP-VEGF Angiogenesis Neuroprotection Molecular therapy |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109003040 |
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