6533b7d6fe1ef96bd1265bac

RESEARCH PRODUCT

Simultaneous Boron Ion‐Channel/Growth Factor Receptor Activation for Enhanced Vascularization

Manuel Salmerón-sánchezManuel Salmerón-sánchezPatricia RicoMarcos De La PeñaMercedes CostellVladimira MoulisovaVladimira MoulisovaAleixandre Rodrigo-navarro

subject

0301 basic medicineIntegrinsVEGF receptorsBiomedical EngineeringEuropean Regional Development FundLibrary scienceBoron ionGeneral Biochemistry Genetics and Molecular BiologyBiomaterials03 medical and health sciencesNaBC10302 clinical medicineGrowth factor receptorPolitical scienceFibronectinbiologyEuropean researchVascularizationChick embryosVEGFEngineering and Physical Sciences030104 developmental biologyResearch councilFISICA APLICADA030220 oncology & carcinogenesisbiology.proteinCam assay

description

[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.

yearjournalcountryeditionlanguage
2018-10-30Advanced Biosystems
https://doi.org/10.1002/adbi.201800220