repair in animal model of emphysema.

Abstract Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report β1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against β1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of β 1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of β1 integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of β1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue.