The proprotein convertase furin inhibits IL-13-induced inflammation in airway smooth muscle by regulating integrin-associated signaling complexes.
Am J Physiol Lung Cell Mol Physiol
; 321(1): L102-L115, 2021 07 01.
Article
em En
| MEDLINE
| ID: mdl-34009050
ABSTRACT
Furin is a proprotein convertase that regulates the activation and the inactivation of multiple proteins including matrix metalloproteinases, integrins, and cytokines. It is a serine endoprotease that localizes to the plasma membrane and can be secreted into the extracellular space. The role of furin in regulating inflammation in isolated canine airway smooth muscle tissues was investigated. The treatment of airway tissues with recombinant furin (rFurin) inhibited the activation of Akt and eotaxin secretion induced by IL-13, and it prevented the IL-13-induced suppression of smooth muscle myosin heavy chain expression. rFurin promoted a differentiated phenotype by activating ß1-integrin proteins and stimulating the activation of the adhesome proteins vinculin and paxillin by talin. Activated paxillin induced the binding of Akt to ß-parvin IPP [integrin-linked kinase (ILK), PINCH, parvin] complexes, which inhibits Akt activation. Treatment of tissues with a furin inhibitor or the depletion of endogenous furin using shRNA resulted in Akt activation and inflammatory responses similar to those induced by IL-13. Furin inactivation or IL-13 caused talin cleavage and integrin inactivation, resulting in the inactivation of vinculin and paxillin. Paxillin inactivation resulted in the coupling of Akt to α-parvin IPP complexes, which catalyze Akt activation and an inflammatory response. The results demonstrate that furin inhibits inflammation in airway smooth muscle induced by IL-13 and that the anti-inflammatory effects of furin are mediated by activating integrin proteins and integrin-associated signaling complexes that regulate Akt-mediated pathways to the nucleus. Furin may have therapeutic potential for the treatment of inflammatory conditions of the lungs and airways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traqueia
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Integrinas
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Interleucina-13
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Furina
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Inflamação
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Músculo Liso
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article