Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.
FASEB J
; 32(3): 1250-1264, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29122847
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound-healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane-anchored serine protease human airway trypsin-like protease (HAT). In the present study, we show that both HAT expression and activity were up-regulated in human IPF specimens. Next, adenoviral overexpression of HAT before bleomycin challenge attenuated lung injury as well as extracellular matrix deposition in the bleomycin-induced pulmonary fibrosis model. In vitro, HAT prevented specific fibrosis-associated responses in primary human pulmonary fibroblasts and induced the expression of mediators associated with the prostaglandin E2 pathway. Altogether, our findings suggested that HAT could have a protective role in IPF and other fibrotic lung disorders.-Menou, A., Flajolet, P., Duitmen, J., Justet, A., Moog, S., Jaillet, M., Tabèze, L., Solhonne, B., Garnier, M., Mal, H., Mordant, P., Castier, Y., Cazes, A., Sallenave, J.-M., Mailleux, A. A., Crestani, B. Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
/
Serina Endopeptidases
/
Lesão Pulmonar
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França