# Integrin α5β1 mediates the inhibitory effects of vasoinhibin on angiogenesis and vascular permeability[image]

## TL;DR

This study identifies integrin α5β1 as the receptor through which vasoinhibin inhibits blood vessel growth and permeability, revealing a new mechanism for controlling angiogenesis.

## Contribution

The paper discovers integrin α5β1 as the molecular target of vasoinhibin and unveils a novel integrin activation mechanism that suppresses angiogenesis.

## Key findings

- Vi binds to integrin α5β1 via the HGR motif, and silencing α5β1 blocks Vi's antiangiogenic effects in vitro.
- An antibody against integrin α5β1 prevents Vi's antiangiogenic activity in vivo.
- The HGR motif activates integrin α5β1, increasing endothelial cell adhesion to fibronectin.

## Abstract

Vasoinhibin (Vi) exerts potent inhibitory effects on angiogenesis and vascular permeability through a minimal three-amino acid sequence, the HGR motif. However, the nature of the Vi receptor has remained controversial. Here, we identify integrin α5β1 as the endothelial cell-surface binding molecule mediating the actions of the HGR motif. Vi binds to α5β1 integrin through this motif, and silencing the integrin α5 subunit abolishes the Vi-mediated inhibition of endothelial cell proliferation, invasion, permeability, and tube formation in vitro. Likewise, an antibody against integrin α5β1 prevented the antiangiogenic activity of Vi in the Matrigel plug assay in vivo. Notably, the HGR motif activates integrin α5β1, as reflected by an increase in endothelial cell adhesion to fibronectin, the canonical ligand of integrin α5β1. These findings identify integrin α5β1 as the molecular target of Vi mediating its antiangiogenic and antivasopermeability actions. Furthermore, a novel integrin activation mechanism leading to suppressed angiogenesis is unveiled, thereby challenging the conventional integrin inhibition approach as a therapeutic intervention.