Gene transfer of an engineered transcription factor promoting expression of VEGF-A protects against experimental diabetic neuropathy.
Diabetes
; 55(6): 1847-54, 2006 Jun.
Article
in En
| MEDLINE
| ID: mdl-16731852
ABSTRACT
Peripheral neuropathy is a common, irreversible complication of diabetes. We investigated whether gene transfer of an engineered zinc finger protein transcription factor (ZFP-TF) designed to upregulate expression of the endogenous vascular endothelial growth factor (VEGF)-A gene could protect against experimental diabetic neuropathy. ZFP-TF-driven activation of the endogenous gene results in expression of all of the VEGF-A isoforms, a fact that may be of significance for recapitulation of the proper biological responses stimulated by this potent neuroprotective growth factor. We show here that this engineered ZFP-TF activates VEGF-A in appropriate cells in culture and that the secreted VEGF-A protein induced by the ZFP protects neuroblastoma cell lines from a serum starvation insult in vitro. Importantly, single and repeat intramuscular injections of formulated plasmid DNA encoding the VEGF-A-activating ZFP-TF resulted in protection of both sensory and motor nerve conduction velocities in a streptozotocin-induced rat model of diabetes. These data suggest that VEGF-A-activating ZFP-TFs may ultimately be of clinical utility in the treatment of this disease.
Search on Google
Database:
MEDLINE
Main subject:
Transcription Factors
/
Genetic Therapy
/
Zinc Fingers
/
Vascular Endothelial Growth Factor A
/
Diabetic Neuropathies
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Year:
2006
Type:
Article