BMP4 induces an epithelial-mesenchymal transition-like response in adult airway epithelial cells.
Bone morphogenetic proteins (BMPs) are critical morphogens and play key roles in epithelial-mesenchymal transitions (EMTs) during embryogenesis. BMP4 is required for early mesoderm formation and also regulates morphogenesis and epithelial cell differentiation in developing lungs. While, BMP signalling pathways are activated during lung inflammation in adult mice, the role of BMPs in adult lungs remains unclear. We hypothesised that BMPs are involved in remodelling processes in adult lungs and investigated effects of BMP4 on airway epithelial cells. BEAS-2B cell growth decreased in the presence of BMP4. Cells acquired a mesenchymal-like morphology with downregulation of adherens junction proteins and increased cell motility. Changes in extracellular matrix-related gene expression occurred with BMP4 treatment including upregulation of collagens, fibronectin and tenascin C. We conclude that the activity of BMP4 in EMT during development is recapitulated in adult airway epithelial cells and suggest that this activity may contribute to inflammation and fibrosis in vivo.
Molloy
Emer L
EL
Institute of Immunology, Biology Department, National University of Ireland, Maynooth, Ireland.
Adams
Aine
A
Moore
J Bernadette
JB
Masterson
Joanne C
JC
Madrigal-Estebas
Laura
L
Mahon
Bernard P
BP
O'Dea
Shirley
S
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D015820:Cadherins