Transglutaminase 2: a new player in bronchopulmonary dysplasia?
Eur Respir J
; 44(1): 109-21, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24603819
ABSTRACT
Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD. Transglutaminase expression and localisation were assessed by RT-PCR, immunoblotting, activity assay and immunohistochemical analyses of human and mouse lung tissues. Transglutaminase regulation by transforming growth factor (TGF)-ß was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-ß signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-ß mediated the hyperoxia-induced changes in transglutaminase expression. Transglutaminase 2 expression was upregulated in the lungs of preterm infants with BPD and in the lungs of hyperoxia-exposed mouse pups, where lung development was arrested. Transglutaminase 2 localised to the developing alveolar septa. TGF-ß was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-ß signalling partially restored normal lung structure and normalised lung transglutaminase 2 mRNA expression. Our data point to a role for perturbed transglutaminase 2 activity in the arrested alveolarisation associated with BPD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Displasia Broncopulmonar
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Regulação Enzimológica da Expressão Gênica
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Transglutaminases
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Proteínas de Ligação ao GTP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article