Respiratory failure due to differentiation arrest and expansion of alveolar cells following lung-specific loss of the transcription factor C/EBPα in mice

Daniela S. Bassères, Elena Levantini, Hongbin Ji, Stefano Monti, Shannon Elf, Tajhal Dayaram, Maris Fenyus, Olivier Kocher, Todd Golub, Kwok Kin Wong, Balazs Halmos, Daniel G. Tenen

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The leucine zipper family transcription factor CCAAT enhancer binding protein alpha (C/EBPα) inhibits proliferation and promotes differentiation in various cell types. In this study, we show, using a lung-specific conditional mouse model of C/TEBPα deletion, that loss of C/EBPα in the respiratory epithelium leads to respiratory failure at birth due to an arrest in the type II alveolar cell differentiation program. This differentiation arrest results in the lack of type I alveolar cells and differentiated surfactant-secreting type II alveolar cells. In addition to showing a block in type II cell diferentiation, the neonatal lungs display increased numbers of proliferating cells and decreased numbers of apoptotic cells, leading to epithelial expansion and loss of airspace. Consistent with the phenotype observed, genes associated with alveolar maturation, survival, and proliferation were differentially expressed. Taken together, these results identify C/EBPα as a master regulator of airway epithelial maturation and suggest that the loss of C/EBPα could also be an important event in the multistep process of lung tumorigenesis. Furthermore, this study indicates that exploring the C/EBPα pathway might have therapeutic benefits for patients with respiratory distress syndromes.

Original languageEnglish (US)
Pages (from-to)1109-1123
Number of pages15
JournalMolecular and cellular biology
Volume26
Issue number3
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Bassères, D. S., Levantini, E., Ji, H., Monti, S., Elf, S., Dayaram, T., Fenyus, M., Kocher, O., Golub, T., Wong, K. K., Halmos, B., & Tenen, D. G. (2006). Respiratory failure due to differentiation arrest and expansion of alveolar cells following lung-specific loss of the transcription factor C/EBPα in mice. Molecular and cellular biology, 26(3), 1109-1123. https://doi.org/10.1128/MCB.26.3.1109-1123.2006