Simultaneous boron ion-channel/growth factor receptor activation for enhanced vascularization

[EN] Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here we propose a 3D molecular model for NaBC1 and show that simultaneous stimulation of NaBC1 and vascular growth factor receptors...

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Bibliographic Details
Authors: Rico Tortosa, Patricia María, La Peña Del Rivero, Marcos De|||0000-0002-7949-8459, Rodrigo Navarro, Aleixandre, Moulisova, Vladimira, Costell, Mercedes, Salmerón Sánchez, Manuel
Format: article
Publication Date:2018
Country:España
Institution:Universitat Politècnica de València (UPV)
Repository:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Language:English
OAI Identifier:oai:riunet.upv.es:10251/146286
Online Access:https://riunet.upv.es/handle/10251/146286
Access Level:Open access
Keyword:NaBC1
Boron ion
VEGF
Vascularization
Fibronectin
Integrins
FISICA APLICADA
Description
Summary:[EN] Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here we propose a 3D molecular model for NaBC1 and show that simultaneous stimulation of NaBC1 and vascular growth factor receptors (VEGFR) promote angiogenesis in vitro and in vivo with ultra-low concentrations of VEGF. We show Human Umbilical Vein Endothelial Cells (HUVEC) organization into tubular structures indicative of vascularization potential. Enhanced cell sprouting was found only in the presence of VEGF and boron, effect abrogated after blocking NaBC1. We demonstrate that stimulated NaBC1 promotes angiogenesis via PI3k-independent pathways and that ¿5ß1/¿vß3-integrin binding is not essential to enhanced HUVEC organization. We describe a novel vascularization mechanism that involves the crosstalk and colocalization between NaBC1/VEGFR receptors. This has important translational consequences: just by administering boron, taking advantage of endogenous VEGF, in vivo vascularization is shown in a chorioallantoic membrane assay.

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