Class
Article
College
College of Science
Department
English Department
Faculty Mentor
Irina Polejaeva
Presentation Type
Poster Presentation
Abstract
Due to various mutations, the loss of cystic fibrosis transmembrane conductance regulator (CFTR) function causes cystic fibrosis (CF), predisposing the lungs to chronic infection and inflammation. In young infants with CF, structural airway defects are increasingly recognized before the onset of significant lung disease, which suggests a developmental origin and a possible role in lung disease pathogenesis. The function of CFTR in lung development is unclear and developmental studies in humans with CF are not feasible. Young CF sheep show similar lung development and spontaneous postnatal lung disease similar to humans impacted by CF. We studied lung development in the sheep model (non-CF and CF). At early developmental stages, budding CF airways had smaller, hypo-distended lumens than non-CF airways. Non-CF lung explants exhibited airway lumen distension in response to forskolin/IBMX and fibroblast growth factor (FGF)-10, consistent with CFTR-dependent anion transport/secretion; this was lacking in CF airways. Our results suggest that the CF proximal airway defects originate during branching morphogenesis and that the lack of CFTR-dependent anion transport/liquid secretion likely contributes to these deformities.
Location
Logan, UT
Start Date
4-8-2022 12:00 AM
Included in
Impacts of CFTR Mutations on Pulmonary Development in Sheep
Logan, UT
Due to various mutations, the loss of cystic fibrosis transmembrane conductance regulator (CFTR) function causes cystic fibrosis (CF), predisposing the lungs to chronic infection and inflammation. In young infants with CF, structural airway defects are increasingly recognized before the onset of significant lung disease, which suggests a developmental origin and a possible role in lung disease pathogenesis. The function of CFTR in lung development is unclear and developmental studies in humans with CF are not feasible. Young CF sheep show similar lung development and spontaneous postnatal lung disease similar to humans impacted by CF. We studied lung development in the sheep model (non-CF and CF). At early developmental stages, budding CF airways had smaller, hypo-distended lumens than non-CF airways. Non-CF lung explants exhibited airway lumen distension in response to forskolin/IBMX and fibroblast growth factor (FGF)-10, consistent with CFTR-dependent anion transport/secretion; this was lacking in CF airways. Our results suggest that the CF proximal airway defects originate during branching morphogenesis and that the lack of CFTR-dependent anion transport/liquid secretion likely contributes to these deformities.