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

Journal Contribution - Journal Article

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 neuro- and vasculo-protective 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 hind limb skin, they were not essential for nerve function or vascularisation 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, addition of the VEGF-B isoform, VEGF-B186, to DRG cultures antagonized neuronal stress, maintained the mitochondrial membrane potential and stimulated neuronal survival. Mice overexpressing VEGF-B186 or Flt1 selectively in neurons were protected against the distal neuropathy, whereas exogenous VEGF-B186, 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.
Journal: FASEB JOURNAL
ISSN: 0892-6638
Issue: 5
Volume: 25
Pages: 1461 - 1473
Publication year:2011
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:6
CSS-citation score:1
Authors:International
Authors from:Private, Higher Education
Accessibility:Closed