Bone morphogenetic protein signalling in airway epithelial cells during regeneration

Masterson, Joanne C. and Molloy, Emer L. and Gilbert, Jennifer L. and McCormack, Natasha and Adams, Aine and O'Dea, Shirley (2011) Bone morphogenetic protein signalling in airway epithelial cells during regeneration. Cellular Signalling, 23 (2). ISSN 0898-6568

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Mechanisms of lung regeneration after injury remain poorly understood. Bone morphogenetic protein 4 (BMP4) is critical for lung morphogenesis and regulates differentiation of the airway epithelium during development, although its mechanism of action is unknown. The role of BMPs in adult lungs is unclear. We hypothesised that BMP signalling is involved in regeneration of damaged adult airways after injury. Our aims were to characterise the regeneration process in 1-nitronaphthalene (1-NN) injured airways, to determine if and when BMP signalling is activated during this process and investigate the effects of BMP4 on normal adult airway epithelial cells (AECs). Rats were injected with 50 mg/kg 1-NN and protein expression in AECs was examined by Western blotting of lung lysis lavage, and by immunofluorescence, at 6, 24, 48 and 96 h post injection. Expression of signalling molecules p-ERK-1, p-ERK-2 and p-Smad1/5/8 in AECs peaked at 6 h post injection, coincident with maximal inflammation and prior to airway denudation which occurred at 24 h. While airways were re-epithelialised by 48 h, AEC proliferation peaked later at 96 h post 1-NN injection. In vitro, BMP4 induced a mesenchymal-like morphology in normal AECs, downregulated E-cadherin expression and increased migration in a wound closure assay. Thus, following acute injury, increased BMP signalling in AECs coincides with inflammation and precedes airway denudation and re-epithelialisation. Our data indicate that, similar to its role in controlling tissue architecture during development, BMP signalling regulates regeneration of the airways following acute injury, involving downregulation of E-cadherin and induction of migration in AECs

Item Type: Article
Keywords: Airway; Regeneration; Migration; BMP; Smad; 1-Nitronaphthalene;
Academic Unit: Faculty of Science and Engineering > Research Institutes > Institute of Immunology
Item ID: 2827
Identification Number: 10.1016/j.cellsig.2010.10.010
Depositing User: Dr. Shirley O'Dea
Date Deposited: 15 Nov 2011 11:58
Journal or Publication Title: Cellular Signalling
Publisher: Elsevier
Refereed: Yes

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