Title: Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons
Authors: 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 # ×
Issue Date: May-2011
Publisher: The Federation of American Societies for Experimental Biology
Series Title: FASEB Journal vol:25 issue:5 pages: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 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.
ISSN: 0892-6638
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
* (joint) first author
× corresponding author
# (joint) last author

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