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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents



ID: 711844.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
Transglutaminase 2: a new player in bronchopulmonary dysplasia?
Authors:Witsch, T. J.; Niess, G.; Sakkas, E.; Likhoshvay, T.; Becker, S.; Herold, S.; Mayer, K.; Vadasz, I.; Roberts, J. D.; Seeger, W.; Morty, R. E.
Date of Publication (YYYY-MM-DD):2014-07
Title of Journal:Eur Respir J
Volume:44
Issue / Number:1
Start Page:109
End Page:121
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals; Bronchopulmonary Dysplasia/*metabolism/mortality; Epithelial Cells/cytology; Extracellular Matrix/metabolism; Female; GTP-Binding Proteins/*metabolism; Gene Expression Regulation; *Gene Expression Regulation, Enzymologic; Humans; Hyperoxia/metabolism; Infant; Infant, Newborn; Infant, Premature; Lung/metabolism; Male; Mice; Pulmonary Alveoli/metabolism; Signal Transduction; Transforming Growth Factor beta/metabolism; Transglutaminases/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Dept of Internal Medicine, University of Giessen and Marburg Lung Center, Giessen Dept of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA, USA. Dept of Internal Medicine, University of Giessen and Marburg Lung Center, Giessen Dept of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany rory.morty@mpi-bn.mpg.de. %^ 1435822045
Identifiers:ISSN:1399-3003 (Electronic) 0903-1936 (Linking) %R 10.1183/09031936.00075713
URL:http://www.ncbi.nlm.nih.gov/pubmed/24603819
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