[HTML][HTML] CFTR and Wnt/beta-catenin signaling in lung development

JC Cohen, JE Larson, E Killeen, D Love… - BMC developmental …, 2008 - Springer
JC Cohen, JE Larson, E Killeen, D Love, KI Takemaru
BMC developmental biology, 2008Springer
Background Cystic fibrosis transmembrane conductance regulator (CFTR) was shown
previously to modify stretch induced differentiation in the lung. The mechanism for CFTR
modulation of lung development was examined by in utero gene transfer of either a sense or
antisense construct to alter CFTR expression levels. The BAT-gal transgenic reporter mouse
line, expressing β-galactosidase under a canonical Wnt/β-catenin-responsive promoter, was
used to assess the relative roles of CFTR, Wnt, and parathyroid hormone-related peptide …
Background
Cystic fibrosis transmembrane conductance regulator (CFTR) was shown previously to modify stretch induced differentiation in the lung. The mechanism for CFTR modulation of lung development was examined by in utero gene transfer of either a sense or antisense construct to alter CFTR expression levels.
The BAT-gal transgenic reporter mouse line, expressing β-galactosidase under a canonical Wnt/β-catenin-responsive promoter, was used to assess the relative roles of CFTR, Wnt, and parathyroid hormone-related peptide (PTHrP) in lung organogenesis. Adenoviruses containing full-length CFTR, a short anti-sense CFTR gene fragment, or a reporter gene as control were used in an intra-amniotic gene therapy procedure to transiently modify CFTR expression in the fetal lung.
Results
A direct correlation between CFTR expression levels and PTHrP levels was found. An inverse correlation between CFTR and Wnt signaling activities was demonstrated.
Conclusion
These data are consistent with CFTR participating in the mechanicosensory process essential to regulate Wnt/β-Catenin signaling required for lung organogenesis.
Springer