期刊
BMC DEVELOPMENTAL BIOLOGY
卷 8, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-213X-8-70
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资金
- NIDDK NIH HHS [R01 DK073191] Funding Source: Medline
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 beta-galactosidase under a canonical Wnt/beta-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/beta-Catenin signaling required for lung organogenesis.
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