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http://hdl.handle.net/1942/11955
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DC Field | Value | Language |
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dc.contributor.author | Dhondt, Joke | - |
dc.contributor.author | PEERAER, Eve | - |
dc.contributor.author | Verheyen, An | - |
dc.contributor.author | Nuydens, Rony | - |
dc.contributor.author | Buysschaert, Ian | - |
dc.contributor.author | Poesen, Koen | - |
dc.contributor.author | Van Geyte, Katie | - |
dc.contributor.author | Beerens, Manu | - |
dc.contributor.author | Shibuya, Masabumi | - |
dc.contributor.author | Haigh, Jody J. | - |
dc.contributor.author | MEERT, Theo | - |
dc.contributor.author | Carmeliet, Peter | - |
dc.contributor.author | Lambrechts, Diether | - |
dc.date.accessioned | 2011-05-19T13:04:57Z | - |
dc.date.available | NO_RESTRICTION | - |
dc.date.available | 2011-05-19T13:04:57Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | FASEB JOURNAL, 25(5). p. 1461-1473 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/1942/11955 | - |
dc.description.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 | - |
dc.description.sponsorship | D. L. is supported by the Research Foundation Flanders, Belgium; J.D. and K. P. are supported by the Institute for the Promotion of Innovation by Science and Technology in Flanders. P. C. is supported by grants from the Geneeskundige stichting Koningin Elisabeth, and by the Muscular Dystrophy Association. This project is partly funded by a research and development grant of the governmental Institute for Science and Technology (IWT) for the promotion of research between universities (D. L., Katholieke Universiteit Leuven) and industry (T. M. and R.N., Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium). | - |
dc.language.iso | en | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.subject.other | neurovascular link; distal neuropathy | - |
dc.subject.other | neurovascular link; distal neuropathy | - |
dc.title | Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 1473 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | 1461 | - |
dc.identifier.volume | 25 | - |
local.format.pages | 13 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | [Lambrechts, Diether] Katholieke Univ Leuven, Vesalius Res Ctr, Flanders Inst Biotechnol, B-3000 Louvain, Belgium. [Dhondt, Joke; Verheyen, An; Buysschaert, Ian; Poesen, Koen; Van Geyte, Katie; Beerens, Manu; Carmeliet, Peter; Lambrechts, Diether] VIB, Vesalius Res Ctr, Louvain, Belgium. [Peeraer, Eve; Verheyen, An; Nuydens, Rony; Meert, Theo] Johnson & Johnson Pharmaceut Res & Dev, Dept Neurosci, Beerse, Belgium. [Peeraer, Eve] Univ Hasselt, Biomed Res Inst, Diepenbeek, Belgium. [Shibuya, Masabumi] Tokyo Med & Dent Univ, Dept Mol Oncol, Tokyo, Japan. [Haigh, Jody J.] VIB, Dept Mol Biomed Res, Vasc Cell Biol Unit, Ghent, Belgium. [Haigh, Jody J.] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. diether.lambrechts@vib-kuleuven.be | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.bibliographicCitation.oldjcat | A1 | - |
dc.identifier.doi | 10.1096/fj.10-170944 | - |
dc.identifier.isi | 000290023800005 | - |
item.fulltext | No Fulltext | - |
item.fullcitation | Dhondt, Joke; PEERAER, Eve; Verheyen, An; Nuydens, Rony; Buysschaert, Ian; Poesen, Koen; Van Geyte, Katie; Beerens, Manu; Shibuya, Masabumi; Haigh, Jody J.; MEERT, Theo; Carmeliet, Peter & Lambrechts, Diether (2011) Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. In: FASEB JOURNAL, 25(5). p. 1461-1473. | - |
item.contributor | Dhondt, Joke | - |
item.contributor | PEERAER, Eve | - |
item.contributor | Verheyen, An | - |
item.contributor | Nuydens, Rony | - |
item.contributor | Buysschaert, Ian | - |
item.contributor | Poesen, Koen | - |
item.contributor | Van Geyte, Katie | - |
item.contributor | Beerens, Manu | - |
item.contributor | Shibuya, Masabumi | - |
item.contributor | Haigh, Jody J. | - |
item.contributor | MEERT, Theo | - |
item.contributor | Carmeliet, Peter | - |
item.contributor | Lambrechts, Diether | - |
item.validation | ecoom 2012 | - |
item.accessRights | Closed Access | - |
crisitem.journal.issn | 0892-6638 | - |
crisitem.journal.eissn | 1530-6860 | - |
Appears in Collections: | Research publications |
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