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Updated: May 17, 2026
09:59
Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
CFTR facilitates fluid secretion by ferret alveolar type 2 cells
Liyuan Yang1, Changfu Yao2, Javahir Hajibabazade3
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, PR China.
Summary
Cystic fibrosis transmembrane conductance regulator (CFTR) in alveolar cells primarily drives fluid secretion, not absorption. This finding aids understanding of CFTR function in lung fluid balance and cystic fibrosis (CF) disease.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Genetics
Background:
- The role of cystic fibrosis transmembrane conductance regulator (CFTR) in alveolar type 2 (AT2) cells regarding lung fluid balance is debated.
- Some research suggests CFTR facilitates fluid absorption, while others indicate a role in fluid secretion.
Purpose of the Study:
- To investigate the function of CFTR in ferret AT2 cells.
- To determine CFTR's role in chloride and fluid transport in the distal lung.
- To assess the impact of CFTR potentiation on apical surface liquid (ASL) homeostasis.
Main Methods:
- Established organoid and air-liquid interface (ALI) cultures from primary ferret AT2 cells.
- Utilized single-cell RNA sequencing (scRNA-seq) for cellular characterization.
- Examined CFTR function, chloride/fluid transport, and ASL volume regulation using pharmacologic CFTR potentiation.
Main Results:
- Organoids comprised >99% AT2 and transitional AT2 cells.
- CFTR-dependent fluid secretion was observed in wild-type organoids, absent in CFTR-G551D cystic fibrosis (CF) organoids, and rescued by VX-770 (Ivacaftor).
- CF ALI cultures showed impaired CFTR-mediated chloride secretion, partially restored by VX-770, with reduced ASL height also improved.
Conclusions:
- CFTR in ferret AT2-derived cultures primarily mediates chloride and fluid secretion, not absorption.
- This in vitro model system offers insights into CFTR's distal lung functions and CF pathogenesis.
- The model serves as a platform for testing CFTR-targeting therapeutics.
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