PT  - JOURNAL ARTICLE
AU  - Thilo J. Witsch
AU  - Gero Niess
AU  - Elpidoforos Sakkas
AU  - Tatyana Likhoshvay
AU  - Simone Becker
AU  - Susanne Herold
AU  - Konstantin Mayer
AU  - István Vadász
AU  - Jesse D. Roberts, Jr
AU  - Werner Seeger
AU  - Rory E. Morty
TI  - Transglutaminase 2: a new player in bronchopulmonary dysplasia?
AID  - 10.1183/09031936.00075713
DP  - 2014 Jul 01
TA  - European Respiratory Journal
PG  - 109--121
VI  - 44
IP  - 1
4099  - http://erj.ersjournals.com/content/44/1/109.short
4100  - http://erj.ersjournals.com/content/44/1/109.full
SO  - Eur Respir J2014 Jul 01; 44
AB  - 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)-β was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-β signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-β 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-β was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-β 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. Transglutaminase 2 may be a novel pathogenic factor in arrested lung development associated with BPD http://ow.ly/t7kMi