Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

B. Oosthuyse; L. Moons; E. Storkebaum; H. Beck; D. Nuyens; K. Brusselmans; J. van Dorpe; P. Hellings; M. Gorselink; S. Heymans; G Theilmeier; M. Dewerchin; V. Laudenbach; P. Vermylen; H. Raat; T. Acker; V. Vleminckx; L. van den Bosch; N. Cashman; H. Fujisawa; M. Drost; R. Sciot; F. Bruyninckx; Daniel J. Hicklin; C. Ince; P. Gressens; F. Lupu; K.H. Plate; W. Robberecht; J.M. Herbert; D. Collen; P. Carmeliet

doi:10.1038/88842

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

B. Oosthuyse, L. Moons, E. Storkebaum, H. Beck, D. Nuyens, K. Brusselmans, J. van Dorpe, P. Hellings, M. Gorselink, S. Heymans, G Theilmeier, M. Dewerchin, V. Laudenbach, P. Vermylen, H. Raat, T. Acker, V. Vleminckx, L. van den Bosch, N. Cashman, H. FujisawaM. Drost, R. Sciot, F. Bruyninckx, Daniel J. Hicklin, C. Ince, P. Gressens, F. Lupu, K.H. Plate, W. Robberecht, J.M. Herbert, D. Collen, P. Carmeliet^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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. Vegf(165) 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.

Original language	English
Pages (from-to)	131-138
Number of pages	8
Journal	Nature Genetics
Volume	28
Issue number	2
DOIs	https://doi.org/10.1038/88842
Publication status	Published - 1 Jan 2001

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Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., van Dorpe, J., Hellings, P., Gorselink, M., Heymans, S., Theilmeier, G., Dewerchin, M., Laudenbach, V., Vermylen, P., Raat, H., Acker, T., Vleminckx, V., van den Bosch, L., Cashman, N., ... Carmeliet, P. (2001). Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nature Genetics, 28(2), 131-138. https://doi.org/10.1038/88842

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title = "Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration",

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. Vegf(165) 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.",

author = "B. Oosthuyse and L. Moons and E. Storkebaum and H. Beck and D. Nuyens and K. Brusselmans and {van Dorpe}, J. and P. Hellings and M. Gorselink and S. Heymans and G Theilmeier and M. Dewerchin and V. Laudenbach and P. Vermylen and H. Raat and T. Acker and V. Vleminckx and {van den Bosch}, L. and N. Cashman and H. Fujisawa and M. Drost and R. Sciot and F. Bruyninckx and Hicklin, {Daniel J.} and C. Ince and P. Gressens and F. Lupu and K.H. Plate and W. Robberecht and J.M. Herbert and D. Collen and P. Carmeliet",

year = "2001",

month = jan,

day = "1",

doi = "10.1038/88842",

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issn = "1061-4036",

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Oosthuyse, B, Moons, L, Storkebaum, E, Beck, H, Nuyens, D, Brusselmans, K, van Dorpe, J, Hellings, P, Gorselink, M, Heymans, S, Theilmeier, G, Dewerchin, M, Laudenbach, V, Vermylen, P, Raat, H, Acker, T, Vleminckx, V, van den Bosch, L, Cashman, N, Fujisawa, H, Drost, M, Sciot, R, Bruyninckx, F, Hicklin, DJ, Ince, C, Gressens, P, Lupu, F, Plate, KH, Robberecht, W, Herbert, JM, Collen, D & Carmeliet, P 2001, 'Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration', Nature Genetics, vol. 28, no. 2, pp. 131-138. https://doi.org/10.1038/88842

TY - JOUR

T1 - Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

AU - Oosthuyse, B.

AU - Moons, L.

AU - Storkebaum, E.

AU - Beck, H.

AU - Nuyens, D.

AU - Brusselmans, K.

AU - van Dorpe, J.

AU - Hellings, P.

AU - Gorselink, M.

AU - Heymans, S.

AU - Theilmeier, G

AU - Dewerchin, M.

AU - Laudenbach, V.

AU - Vermylen, P.

AU - Raat, H.

AU - Acker, T.

AU - Vleminckx, V.

AU - van den Bosch, L.

AU - Cashman, N.

AU - Fujisawa, H.

AU - Drost, M.

AU - Sciot, R.

AU - Bruyninckx, F.

AU - Hicklin, Daniel J.

AU - Ince, C.

AU - Gressens, P.

AU - Lupu, F.

AU - Plate, K.H.

AU - Robberecht, W.

AU - Herbert, J.M.

AU - Collen, D.

AU - Carmeliet, P.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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. Vegf(165) 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.

AB - 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. Vegf(165) 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.

U2 - 10.1038/88842

DO - 10.1038/88842

M3 - Article

SN - 1061-4036

VL - 28

SP - 131

EP - 138

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -