| Registro completo |
| Provedor de dados: |
Nature Precedings
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| País: |
United Kingdom
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| Título: |
Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.
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| Autores: |
Rehab J. Al-Jamal
Linda Wilson
Chris J. Armit
Susan McIntyre
Mark Marsden
Steven D. Shapiro
David J. Harrison
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| Data: |
2007-07-12
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| Ano: |
2007
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| Palavras-chave: |
Pharmacology
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| Resumo: |
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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| Tipo: |
Manuscript
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| Identificador: |
http://precedings.nature.com/documents/437/version/1
oai:nature.com:10101/npre.2007.437.1
http://hdl.handle.net/10101/npre.2007.437.1
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| Fonte: |
Nature Precedings
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| Direitos: |
Creative Commons Attribution 3.0 License
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