Postnatal airway growth in cystic fibrosis piglets

被引:5
作者
Adam, Ryan J. [1 ,2 ]
Abou Alaiwa, Mahmoud H. [1 ]
Bouzek, Drake C. [1 ]
Cook, Daniel P. [1 ]
Gansemer, Nicholas D. [1 ]
Taft, Peter J. [1 ]
Powers, Linda S. [1 ]
Stroik, Mallory R. [1 ]
Hoegger, Mark J. [1 ]
McMenimen, James D. [1 ]
Hoffman, Eric A. [1 ,2 ,5 ]
Zabner, Joseph [1 ,6 ]
Welsh, Michael J. [1 ,3 ,6 ,7 ]
Meyerholz, David K. [4 ]
Stoltz, David A. [1 ,2 ,3 ,6 ]
机构
[1] Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Biomed Engn, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[3] Univ Iowa, Dept Mol Physiol & Biophys, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA
[4] Univ Iowa, Dept Pathol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[5] Univ Iowa, Dept Radiol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[6] Univ Iowa, Pappajohn Biomed Inst, Iowa City, IA USA
[7] Univ Iowa, Howard Hughes Med Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
基金
美国国家卫生研究院;
关键词
cystic fibrosis; porcine; computed tomography; airway distensibility; TRANSMEMBRANE CONDUCTANCE REGULATOR; SMOOTH-MUSCLE; CFTR EXPRESSION; PORCINE MODEL; LUNG-DISEASE; GENE; DISTENSIBILITY; PIGS; CONTRACTILITY; INFANTS;
D O I
10.1152/japplphysiol.00263.2017
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis.
引用
收藏
页码:526 / 533
页数:8
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