Could an endoneurial endothelial crosstalk between Wnt/ß-catenin and Sonic Hedgehog pathways underlie the early disruption of the infra-orbital blood-nerve barrier following chronic constriction injury?
Mol Pain
; 13: 1744806917727625, 2017.
Article
em En
| MEDLINE
| ID: mdl-28814148
ABSTRACT
Background:
Bloodnerve barrier disruption is pivotal in the development of neuroinflammation, peripheral sensitization, and neuropathic pain after peripheral nerve injury. Activation of toll-like receptor 4 and inactivation of Sonic Hedgehog signaling pathways within the endoneurial endothelial cells are key events, resulting in the infiltration of harmful molecules and immunocytes within the nerve parenchyma. However, we showed in a previous study that preemptive inactivation of toll-like receptor 4 signaling or sustained activation of Sonic Hedgehog signaling did not prevent the local alterations observed following peripheral nerve injury, suggesting the implication of another signaling pathway.Methods:
Using a classical neuropathic pain model, the infraorbital nerve chronic constriction injury (IoN-CCI), we investigated the role of the Wnt/ß-catenin pathway in chronic constriction injury-mediated bloodnerve barrier disruption and in its interactions with the toll-like receptor 4 and Sonic Hedgehog pathways. In the IoN-CCI model versus control, mRNA expression levels and/or immunochemical detection of major Wnt/Sonic Hedgehog pathway (Frizzled-7, vascular endothelial-cadherin, Patched-1 and Gli-1) and/or tight junction proteins (Claudin-1, Claudin-5, and Occludin) readouts were assessed. Vascular permeability was assessed by sodium fluorescein extravasation.Results:
IoN-CCI induced early alterations in the vascular endothelial-cadherin/ß-catenin/Frizzled-7 complex, shown to participate in local bloodnerve barrier disruption via a ß-catenin-dependent tight junction protein downregulation. Wnt pathway also mediated a crosstalk between toll-like receptor 4 and Sonic Hedgehog signaling within endoneurial endothelial cells. Nevertheless, preemptive inhibition of Wnt/ß-catenin signaling before IoN-CCI could not prevent the downregulation of key Sonic Hedgehog pathway readouts or the disruption of the infraorbital bloodnerve barrier, suggesting that Sonic Hedgehog pathway inhibition observed following IoN-CCI is an independent event responsible for bloodnerve barrier disruption.Conclusion:
A crosstalk between Wnt/ß-catenin- and Sonic Hedgehog-mediated signaling pathways within endoneurial endothelial cells could mediate the chronic disruption of the bloodnerve barrier following IoN-CCI, resulting in increased irreversible endoneurial vascular permeability and neuropathic pain development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Endoteliais
/
Barreira Hematoneural
/
Via de Sinalização Wnt
Limite:
Animals
Idioma:
En
Revista:
Mol Pain
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
/
PSICOFISIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França