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

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) n...

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Autores principales:	Michela M Taiana, Raffaella Lombardi, Carla Porretta-Serapiglia, Emilio Ciusani, Norberto Oggioni, Jenny Sassone, Roberto Bianchi, Giuseppe Lauria
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b2791f597b54bca9c0693acaa633db5
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spelling	oai:doaj.org-article:2b2791f597b54bca9c0693acaa633db52021-11-25T05:58:43ZNeutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.1932-620310.1371/journal.pone.0108403https://doaj.org/article/2b2791f597b54bca9c0693acaa633db52014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108403https://doaj.org/toc/1932-6203The 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.Michela M TaianaRaffaella LombardiCarla Porretta-SerapigliaEmilio CiusaniNorberto OggioniJenny SassoneRoberto BianchiGiuseppe LauriaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108403 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michela M Taiana Raffaella Lombardi Carla Porretta-Serapiglia Emilio Ciusani Norberto Oggioni Jenny Sassone Roberto Bianchi Giuseppe Lauria Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.
description	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.
format	article
author	Michela M Taiana Raffaella Lombardi Carla Porretta-Serapiglia Emilio Ciusani Norberto Oggioni Jenny Sassone Roberto Bianchi Giuseppe Lauria
author_facet	Michela M Taiana Raffaella Lombardi Carla Porretta-Serapiglia Emilio Ciusani Norberto Oggioni Jenny Sassone Roberto Bianchi Giuseppe Lauria
author_sort	Michela M Taiana
title	Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.
title_short	Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.
title_full	Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.
title_fullStr	Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.
title_full_unstemmed	Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.
title_sort	neutralization of schwann cell-secreted vegf is protective to in vitro and in vivo experimental diabetic neuropathy.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2b2791f597b54bca9c0693acaa633db5
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Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.

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