Engineered zinc finger protein-mediated VEGF-a activation restores deficient VEGF-a in sensory neurons in experimental diabetes.

Diabetes
Elizabeth J PawsonNatalie J Gardiner

Abstract

The objectives of the study were to evaluate retrograde axonal transport of vascular endothelial growth factor A (VEGF-A) protein to sensory neurons after intramuscular administration of an engineered zinc finger protein activator of endogenous VEGF-A (VZ+434) in an experimental model of diabetes, and to characterize the VEGF-A target neurons. We compared the expression of VEGF-A in lumbar (L)4/5 dorsal root ganglia (DRG) of control rats and VZ+434-treated and untreated streptozotocin (STZ)-induced diabetic rats. In addition, axonal transport of VEGF-A, activation of signal transduction pathways in the DRG, and mechanical sensitivity were assessed. VEGF-A immunoreactivity (IR) was detected in small- to medium-diameter neurons in DRG of control rats. Fewer VEGF-A-IR neurons were observed in DRG from STZ-induced diabetic rats; this decrease was confirmed and quantified by Western blotting. VZ+434 administration resulted in a significant increase in VEGF-A protein expression in ipsilateral DRG, 24 h after injection. VEGF-A was axonally transported to the DRG via the sciatic nerve. VZ+434 administration resulted in significant activation of AKT in the ipsilateral DRG by 48 h that was sustained for 1 week after injection. VZ+434 pro...Continue Reading

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Citations

Nov 10, 2013·Analytical Chemistry·Byeong-Ui MoonElisabeth Verpoorte
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BETA
PCR
biopsy

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SigmaScan
GraphPad PRISM
WASABI
SigmaScan Pro
SigmaScan Pro5
Adobe Photoshop

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