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bioRxiv · 10.1101/2025.07.13.664588

Integrin α5β1 mediates the inhibitory effects of vasoinhibin on angiogenesis and vascular permeability

Zamora, M.·Clapp, C.·de la Escalera, G. M.·Robles, J. P.
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Abstract

Vasoinhibin exerts potent inhibitory effects on angiogenesis and vascular permeability through a minimal three-amino acid sequence, the HGR motif. However, the nature of the vasoinhibin receptor has remained controversial. Here, we identify integrin 5{beta}1 as the endothelial cell-surface binding molecule mediating the actions of the HGR motif. Vasoinhibin binds to 5{beta}1 integrin through this motif, and silencing the integrin 5 subunit abolishes the vasoinhibin-mediated inhibition of endothelial cell proliferation, invasion, and permeability. Notably, the HGR motif activates integrin 5{beta}1, as reflected by an increase in endothelial cell adhesion to fibronectin, the canonical ligand of integrin 5{beta}1. These findings identify integrin 5{beta}1 as the molecular target of vasoinhibin mediating its antiangiogenic and anti-vasopermeability actions. Furthermore, a novel integrin activation mechanism leading to suppressed angiogenesis is unveiled, thereby challenging the conventional integrin inhibition approach as a therapeutic intervention.

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Zamora, M., Clapp, C., de la Escalera, G. M., Robles, J. P.. 2025-07-14. Integrin α5β1 mediates the inhibitory effects of vasoinhibin on angiogenesis and vascular permeability. https://doi.org/10.1101/2025.07.13.664588

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