β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

The Wnt/β-catenin signaling cascade activates genes that allow cells to adopt particular identities throughout development. In adult self-renewing tissues like intestine and blood, activation of the Wnt pathway maintains a progenitor phenotype, whereas forced inhibition of this pathway promotes diff...

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Bibliographic Details
Published in:The Journal of biological chemistry 2010-01, Vol.285 (5), p.3157-3167
Main Authors: Flozak, Annette S., Lam, Anna P., Russell, Susan, Jain, Manu, Peled, Ofra N., Sheppard, Kerry A., Beri, Rohinee, Mutlu, Gökhan M., Budinger, G.R. Scott, Gottardi, Cara J.
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Bleomycin - pharmacology
Cell Differentiation
Cell Movement
Cell Survival
Cell/Epithelial
Developmental Pathways
Diseases
Epithelial Cells - metabolism
Lung Injury - metabolism
Lung Injury - pathology
Male
Mice
Mice, Inbred C57BL
Molecular Basis of Cell and Developmental Biology
Organisms/Mouse
Pulmonary Alveoli - metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
TCF Transcription Factors - metabolism
Tissue/Organ Systems/Lung
Wnt Signaling
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Summary:The Wnt/β-catenin signaling cascade activates genes that allow cells to adopt particular identities throughout development. In adult self-renewing tissues like intestine and blood, activation of the Wnt pathway maintains a progenitor phenotype, whereas forced inhibition of this pathway promotes differentiation. In the lung alveolus, type 2 epithelial cells (AT2) have been described as progenitors for the type 1 cell (AT1), but whether AT2 progenitors use the same signaling mechanisms to control differentiation as rapidly renewing tissues is not known. We show that adult AT2 cells do not exhibit constitutive β-catenin signaling in vivo, using the AXIN2+/LacZ reporter mouse, or after fresh isolation of an enriched population of AT2 cells. Rather, this pathway is activated in lungs subjected to bleomycin-induced injury, as well as upon placement of AT2 cells in culture. Forced inhibition of β-catenin/T-cell factor signaling in AT2 cultures leads to increased cell death. Cells that survive show reduced migration after wounding and reduced expression of AT1 cell markers (T1α and RAGE). These results suggest that AT2 cells may function as facultative progenitors, where activation of Wnt/β-catenin signaling during lung injury promotes alveolar epithelial survival, migration, and differentiation toward an AT1-like phenotype.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.070326