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Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons

(2011) FASEB JOURNAL. 25(5). p.1461-1473
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Abstract
Even though VEGF-B is a homologue of the potent angiogenic factor VEGF, its angiogenic activities have been controversial. Intrigued by findings that VEGF-B may also affect neuronal cells, we assessed the neuroprotective and vasculoprotective effects of VEGF-B in the skin, in which vessels and nerves are functionally intertwined. Although VEGF-B and its FLT1 receptor were prominently expressed in dorsal root ganglion (DRG) neurons innervating the hindlimb skin, they were not essential for nerve function or vascularization of the skin. However, primary DRG cultures lacking VEGF-B or FLT1 exhibited increased neuronal stress and were more susceptible to paclitaxel-induced cell death. Concomitantly, mice lacking VEGF-B or a functional FLT1 developed more retrograde degeneration of sensory neurons in a model of distal neuropathy. On the other hand, the addition of the VEGF-B isoform, VEGF-B-186, to DRG cultures antagonized neuronal stress, maintained the mitochondrial membrane potential and stimulated neuronal survival. Mice overexpressing VEGF-B-186 or FLT1 selectively in neurons were protected against the distal neuropathy, whereas exogenous VEGF-B-186, either delivered by gene transfer or as a recombinant factor, was protective by directly affecting sensory neurons and not the surrounding vasculature. Overall, this indicates that VEGF-B, instead of acting as an angiogenic factor, exerts direct neuroprotective effects through FLT1. These findings also suggest a clinically relevant role for VEGF-B in preventing distal neuropathies.-Dhondt, J., Peeraer, E., Verheyen, A., Nuydens, R., Buysschaert, I., Poesen, K., Van Geyte, K., Beerens, M., Shibuya, M., Haigh, J. J., Meert, T., Carmeliet, P., Lambrechts, D. Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. FASEB J. 25, 1461-1473 (2011). www.fasebj.org
Keywords
ENDOTHELIAL GROWTH-FACTOR, INDUCED PERIPHERAL NEUROPATHY, DIABETIC-NEUROPATHY, GENE-TRANSFER, ANGIOGENESIS, INJURY, NERVE, EXPRESSION, CANCER, CELLS, neurovascular link, distal neuropathy

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Citation

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Chicago
Dhondt, Joke, Eve Peeraer, An Verheyen, Rony Nuydens, Ian Buysschaert, Koen Poesen, Katie Van Geyte, et al. 2011. “Neuronal FLT1 Receptor and Its Selective Ligand VEGF-B Protect Against Retrograde Degeneration of Sensory Neurons.” Faseb Journal 25 (5): 1461–1473.
APA
Dhondt, Joke, Peeraer, E., Verheyen, A., Nuydens, R., Buysschaert, I., Poesen, K., Van Geyte, K., et al. (2011). Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. FASEB JOURNAL, 25(5), 1461–1473.
Vancouver
1.
Dhondt J, Peeraer E, Verheyen A, Nuydens R, Buysschaert I, Poesen K, et al. Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. FASEB JOURNAL. 2011;25(5):1461–73.
MLA
Dhondt, Joke, Eve Peeraer, An Verheyen, et al. “Neuronal FLT1 Receptor and Its Selective Ligand VEGF-B Protect Against Retrograde Degeneration of Sensory Neurons.” FASEB JOURNAL 25.5 (2011): 1461–1473. Print.
@article{1224306,
  abstract     = {Even though VEGF-B is a homologue of the potent angiogenic factor VEGF, its angiogenic activities have been controversial. Intrigued by findings that VEGF-B may also affect neuronal cells, we assessed the neuroprotective and vasculoprotective effects of VEGF-B in the skin, in which vessels and nerves are functionally intertwined. Although VEGF-B and its FLT1 receptor were prominently expressed in dorsal root ganglion (DRG) neurons innervating the hindlimb skin, they were not essential for nerve function or vascularization of the skin. However, primary DRG cultures lacking VEGF-B or FLT1 exhibited increased neuronal stress and were more susceptible to paclitaxel-induced cell death. Concomitantly, mice lacking VEGF-B or a functional FLT1 developed more retrograde degeneration of sensory neurons in a model of distal neuropathy. On the other hand, the addition of the VEGF-B isoform, VEGF-B-186, to DRG cultures antagonized neuronal stress, maintained the mitochondrial membrane potential and stimulated neuronal survival. Mice overexpressing VEGF-B-186 or FLT1 selectively in neurons were protected against the distal neuropathy, whereas exogenous VEGF-B-186, either delivered by gene transfer or as a recombinant factor, was protective by directly affecting sensory neurons and not the surrounding vasculature. Overall, this indicates that VEGF-B, instead of acting as an angiogenic factor, exerts direct neuroprotective effects through FLT1. These findings also suggest a clinically relevant role for VEGF-B in preventing distal neuropathies.-Dhondt, J., Peeraer, E., Verheyen, A., Nuydens, R., Buysschaert, I., Poesen, K., Van Geyte, K., Beerens, M., Shibuya, M., Haigh, J. J., Meert, T., Carmeliet, P., Lambrechts, D. Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. FASEB J. 25, 1461-1473 (2011). www.fasebj.org},
  author       = {Dhondt, Joke and Peeraer, Eve and Verheyen, An and Nuydens, Rony and Buysschaert, Ian and Poesen, Koen and Van Geyte, Katie and Beerens, Manu and Shibuya, Masabumi and Haigh, Jody and Meert, Theo and Carmeliet, Peter and Lambrechts, Diether},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  keyword      = {ENDOTHELIAL GROWTH-FACTOR,INDUCED PERIPHERAL NEUROPATHY,DIABETIC-NEUROPATHY,GENE-TRANSFER,ANGIOGENESIS,INJURY,NERVE,EXPRESSION,CANCER,CELLS,neurovascular link,distal neuropathy},
  language     = {eng},
  number       = {5},
  pages        = {1461--1473},
  title        = {Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons},
  url          = {http://dx.doi.org/10.1096/fj.10-170944},
  volume       = {25},
  year         = {2011},
}

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