Cohen J Craig, Larson Janet E, Killeen Erin, Love Damon, Takemaru Ken-Ichi
The Brady Laboratory, Section of Neonatology, Department of Pediatrics, Stony Brook University, School of Medicine, Stony Brook, New York, USA.
BMC Dev Biol. 2008 Jul 6;8:70. doi: 10.1186/1471-213X-8-70.
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.
A direct correlation between CFTR expression levels and PTHrP levels was found. An inverse correlation between CFTR and Wnt signaling activities was demonstrated.
These data are consistent with CFTR participating in the mechanicosensory process essential to regulate Wnt/beta-Catenin signaling required for lung organogenesis.
先前已表明囊性纤维化跨膜传导调节因子（CFTR）可调节肺中拉伸诱导的分化。通过子宫内基因转移有义或反义构建体以改变CFTR表达水平，研究了CFTR调节肺发育的机制。利用BAT-gal转基因报告小鼠品系，其在经典Wnt/β-连环蛋白反应性启动子下表达β-半乳糖苷酶，来评估CFTR、Wnt和甲状旁腺激素相关肽（PTHrP）在肺器官发生中的相对作用。含有全长CFTR、短反义CFTR基因片段或作为对照的报告基因的腺病毒用于羊膜内基因治疗程序，以瞬时改变胎儿肺中的CFTR表达。
发现CFTR表达水平与PTHrP水平之间存在直接相关性。证明了CFTR与Wnt信号传导活性之间存在负相关。
这些数据与CFTR参与调节肺器官发生所需的Wnt/β-连环蛋白信号传导所必需的机械感觉过程一致。
