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

Rico, P., Rodrigo-Navarro, A. , De la Pena, M., Moulisova, V., Costell, M. and Salmeron-Sanchez, M. (2018) Simultaneous boron ion-channel/growth factor receptor activation for enhanced vascularization. Advanced Biosystems, (Accepted for Publication)

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Abstract

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 Akt-independent pathways and that α5β1/αvβ3-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.

Item Type:Articles
Status:Accepted for Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Moulisova, Dr Vladimira and Rodrigo-Navarro, Mr Aleixandre
Authors: Rico, P., Rodrigo-Navarro, A., De la Pena, M., Moulisova, V., Costell, M., and Salmeron-Sanchez, M.
College/School:College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Advanced Biosystems
Publisher:Wiley
ISSN:2366-7478
ISSN (Online):2366-7478

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
722061Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - BIOMEDICAL ENGINEERING