ArticleProceedings of the National Academy of Sciences of the United States of America2016
Relationships among CFTR expression, HCO3- secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 77 citations in OpenAlex.
- Risk Carriers: Elevated Risk of Post-ERCP Pancreatitis in Patients Heterozygous for Mutations of the Cystic Firbrosis Transmembrane Regulator (CFTR) Gene.Digestive diseases and sciences · 2026Article
- Cystic Fibrosis Heterozygosity as a Risk Factor for Post-ERCP Pancreatitis: Implications for ERCP Risk Stratification in the Cosmos Cohort.Digestive diseases and sciences · 2026Article
- Article
- Cellular Models and Functional Assays for Assessing CFTR Function: A Comprehensive Review.International journal of molecular sciences · 2026Review
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- The Interface of Gene Editing with Regenerative Medicine.Engineering (Beijing, China) · 2025Article
- Factor 3 regulates airway engraftment by human bronchial basal cells.Stem cells translational medicine · 2025Article
- Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells.Nature biomedical engineering · 2025Article
- DNA-PKcs inhibition improves sequential gene insertion of the full-lengthMolecular therapy. Nucleic acids · 2024Article
- Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.Nucleic acids research · 2024Article
- DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-LengthbioRxiv : the preprint server for biology · 2024Article
- Structural identification of a selectivity filter in CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.Frontiers in physiology · 2024Review
- Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo.Nature communications · 2023Article
- SLC26A9 in airways and intestine: secretion or absorption?Channels (Austin, Tex.) · 2023Review
- Effect of glucose on growth and co-culture ofHeliyon · 2023Article
- ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases.Biomolecules · 2023Review
- Expression of gain-of-function CFTR in cystic fibrosis airway cells restores epithelial function better than wild-type or codon-optimized CFTR.Molecular therapy. Methods & clinical development · 2023Article
- Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins.International journal of molecular sciences · 2023Review
- Targeting ATP12A, a Nongastric Proton Pump α Subunit, for Idiopathic Pulmonary Fibrosis Treatment.American journal of respiratory cell and molecular biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Airway disease is the major source of morbidity and mortality. Successful implementation of gene- and cell-based therapies for CF airway disease requires knowledge of relationships among percentages of targeted cells, levels of CFTR expression, correction of electrolyte transport, and rescue of host defense defects. Previous studies suggested that, when ∼10-50% of airway epithelial cells expressed CFTR, they generated nearly wild-type levels of Cl(-) secretion; overexpressing CFTR offered no advantage compared with endogenous expression levels. However, recent discoveries focused attention on CFTR-mediated HCO3 (-) secretion and airway surface liquid (ASL) pH as critical for host defense and CF pathogenesis. Therefore, we generated porcine airway epithelia with varying ratios of CF and wild-type cells. Epithelia with a 50:50 mix secreted HCO3 (-) at half the rate of wild-type epithelia. Likewise, heterozygous epithelia (CFTR(+/-) or CFTR(+/∆F508)) expressed CFTR and secreted HCO3 (-) at ∼50% of wild-type values. ASL pH, antimicrobial activity, and viscosity showed similar relationships to the amount of CFTR. Overexpressing CFTR increased HCO3 (-) secretion to rates greater than wild type, but ASL pH did not exceed wild-type values. Thus, in contrast to Cl(-) secretion, the amount of CFTR is rate-limiting for HCO3 (-) secretion and for correcting host defense abnormalities. In addition, overexpressing CFTR might produce a greater benefit than expressing CFTR at wild-type levels when targeting small fractions of cells. These findings may also explain the risk of airway disease in CF carriers.
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