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

Tijdschriftbijdrage - Tijdschriftartikel

Even though VEGF-B is a homologue of the potent angiogenic factor VEGF, itsangiogenic activities have been controversial. Intrigued by findings that VEGF-B may alsoaffect neuronal cells, we assessed the neuro- and vasculo-protective effects of VEGF-B inthe skin, in which vessels and nerves are functionally intertwined.Although VEGF-B and its Flt1 receptor were prominently expressed in dorsal rootganglion (DRG) neurons innervating the hind limb skin, they were not essential for nervefunction or vascularisation of the skin. However, primary DRG cultures lacking VEGF-B orFlt1 exhibited increased neuronal stress and were more susceptible to paclitaxel-inducedcell death. Concomitantly, mice lacking VEGF-B or a functional Flt1 developed moreretrograde degeneration of sensory neurons in a model of distal neuropathy. On the otherhand, addition of the VEGF-B isoform, VEGF-B186, to DRG cultures antagonized neuronalstress, maintained the mitochondrial membrane potential and stimulated neuronal survival.Mice overexpressing VEGF-B186 or Flt1 selectively in neurons were protected against thedistal neuropathy, whereas exogenous VEGF-B186, either delivered by gene transfer or asa recombinant factor, was protective by directly affecting sensory neurons and not thesurrounding vasculature.Overall, this indicates that VEGF-B, instead of acting as an angiogenic factor, exertsdirect neuroprotective effects through Flt1. These findings also suggest a clinically relevantrole for VEGF-B in preventing distal neuropathies.
Tijdschrift: FASEB Journal
ISSN: 0892-6638
Issue: 5
Volume: 25
Pagina's: 1461 - 1473
Jaar van publicatie:2011