Journal article

Publication year: 2014

Pages: 109-121

Journal: European Respiratory Journal

Volume number: 44

Issue number: 1

ISSN: 0903-1936

eISSN: 1399-3003

Open access status: Green

DOI Link: https://doi.org/10.1183/09031936.00075713

Publisher: European Respiratory Society

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)-beta was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-beta signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-beta 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-beta was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-beta 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.

Harvard Citation style: Witsch, T., Niess, G., Sakkas, E., Likhoshvay, T., Becker, S., Herold, S., et al. (2014) Transglutaminase 2: a new player in bronchopulmonary dysplasia?, European Respiratory Journal, 44(1), pp. 109-121. https://doi.org/10.1183/09031936.00075713

APA Citation style: Witsch, T., Niess, G., Sakkas, E., Likhoshvay, T., Becker, S., Herold, S., Mayer, K., Vadasz, I., Roberts, J., Seeger, W., & Morty, R. (2014). Transglutaminase 2: a new player in bronchopulmonary dysplasia?. European Respiratory Journal. 44(1), 109-121. https://doi.org/10.1183/09031936.00075713