Title: Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration
Authors: Oosthuyse, B
Moons, Lieve
Storkebaum, Erik
Beck, H
Nuyens, Dieter
Brusselmans, K
Van Dorpe, Jo
Hellings, Peter
Gorselink, M
Heymans, S
Theilmeier, G
Dewerchin, Mieke
Laudenbach, V
Vermylen, P
Raat, H
Acker, T
Vleminckx, Vicky
Van Den Bosch, Ludo
Cashman, N
Fujisawa, H
Drost, M R
Sciot, Raphael
Bruyninckx, Frans
Hicklin, D J
Ince, C
Gressens, P
Lupu, F
Plate, K H
Robberecht, Wim
Herbert, J M
Collen, Desire
Carmeliet, Peter # ×
Issue Date: Jun-2001
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:28 issue:2 pages:131-138
Abstract: Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Oto-rhino-laryngology
Research Group Experimental Neurology
Translational Cell & Tissue Research
Molecular and Vascular Biology
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Behavioral and Developmental Genetics
Physical Medicine and Revalidation Section (-)
Faculty of Medicine - miscellaneous
Laboratory for Neurobiology
Laboratory of Clinical Immunology
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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