Abstract
Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 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 beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 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.
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Al-Jamal, R., Wilson, L., Armit , C. et al. Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema. . Nat Prec (2007). https://doi.org/10.1038/npre.2007.437.1
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DOI: https://doi.org/10.1038/npre.2007.437.1