β-Catenin/T-cell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells

Annette S. Flozak, Anna P. Lam, Susan Russell, Manu Jain, Ofra N. Peled, Kerry A. Sheppard, Rohinee Beri, Gökhan M. Mutlu, G. R.Scott Budinger, Cara J. Gottardi

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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. Weshow 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 (T1αand 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.

Original languageEnglish (US)
Pages (from-to)3157-3167
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
StatePublished - Jan 29 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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