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

Joke Dhondt, Eve Peeraer, An Verheyen, Rony Nuydens, Ian Buysschaert, Koen Poesen, Katie Van Geyte, Manu Beerens, Masabumi Shibuya and Jody Haigh UGent, et al. (2011) FASEB JOURNAL. 25(5). p.1461-1473
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
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ENDOTHELIAL GROWTH-FACTOR, INDUCED PERIPHERAL NEUROPATHY, DIABETIC-NEUROPATHY, GENE-TRANSFER, ANGIOGENESIS, INJURY, NERVE, EXPRESSION, CANCER, CELLS, neurovascular link, distal neuropathy
journal title
FASEB JOURNAL
Faseb J.
volume
25
issue
5
pages
1461 - 1473
Web of Science type
Article
Web of Science id
000290023800005
JCR category
BIOLOGY
JCR impact factor
5.712 (2011)
JCR rank
7/84 (2011)
JCR quartile
1 (2011)
ISSN
0892-6638
DOI
10.1096/fj.10-170944
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1224306
handle
http://hdl.handle.net/1854/LU-1224306
date created
2011-05-16 13:35:18
date last changed
2012-06-26 14:32:18
@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},
}

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, J., 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.