Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy

Michela M. Taiana, Raffaella Lombardi, Carla Porretta-Serapiglia, Emilio Ciusani, Norberto Oggioni, Jenny Sassone, Roberto Bianchi, Giuseppe Lauria

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Abstract

The pathogenetic role of vascular endothelial growth factor (VEGF) in long-term retinal and kidney complications of diabetes has been demonstrated. Conversely, little is known in diabetic neuropathy. We examined the modulation of VEGF pathway at mRNA and protein level on dorsal root ganglion (DRG) neurons and Schwann cells (SC) induced by hyperglycaemia. Moreover, we studied the effects of VEGF neutralization on hyperglycemic DRG neurons and streptozotocin-induced diabetic neuropathy. Our findings demonstrated that DRG neurons were not affected by the direct exposition to hyperglycaemia, whereas showed an impairment of neurite outgrowth ability when exposed to the medium of SC cultured in hyperglycaemia. This was mediated by an altered regulation of VEGF and FLT-1 receptors. Hyperglycaemia increased VEGF and FLT-1 mRNA without changing their intracellular protein levels in DRG neurons, decreased intracellular and secreted protein levels without changing mRNA level in SC, while reduced the expression of the soluble receptor sFLT-1 both in DRG neurons and SC. Bevacizumab, a molecule that inhibits VEGF activity preventing the interaction with its receptors, restored neurite outgrowth and normalized FLT-1 mRNA and protein levels in co-cultures. In diabetic rats, it both prevented and restored nerve conduction velocity and nociceptive thresholds. We demonstrated that hyperglycaemia early affected neurite outgrowth through the impairment of SC-derived VEGF/FLT-1 signaling and that the neutralization of SC-secreted VEGF was protective both in vitro and in vivo models of diabetic neuropathy.

Original languageEnglish
Article numbere108403
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 30 2014

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diabetic neuropathy
Schwann cells
vascular endothelial growth factors
Diabetic Neuropathies
Schwann Cells
neutralization
Vascular Endothelial Growth Factor A
Spinal Ganglia
Hyperglycemia
hyperglycemia
Neurons
neurons
neurites
Messenger RNA
Proteins
receptors
proteins
Vascular Endothelial Growth Factor Receptor-1
Neural Conduction
Diabetes Complications

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy. / Taiana, Michela M.; Lombardi, Raffaella; Porretta-Serapiglia, Carla; Ciusani, Emilio; Oggioni, Norberto; Sassone, Jenny; Bianchi, Roberto; Lauria, Giuseppe.

In: PLoS One, Vol. 9, No. 9, e108403, 30.09.2014.

Research output: Contribution to journalArticle

Taiana, Michela M. ; Lombardi, Raffaella ; Porretta-Serapiglia, Carla ; Ciusani, Emilio ; Oggioni, Norberto ; Sassone, Jenny ; Bianchi, Roberto ; Lauria, Giuseppe. / Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy. In: PLoS One. 2014 ; Vol. 9, No. 9.
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