ArticleAmerican journal of physiology. Cell physiology2011
Rescue of the mutant CFTR chloride channel by pharmacological correctors and low temperature analyzed by gene expression profiling.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Integrative genomic meta-analysis reveals novel molecular insights into cystic fibrosis and ΔF508-CFTR rescue.Scientific reports · 2020Pooled it
- Effects of GM1 ganglioside and its derivatives on ETI-rescued F508del-CFTR maturation and host-pathogen interactions in cystic fibrosis bronchial cells.Glycoconjugate journal · 2025Article
- Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators.iScience · 2025Article
- Target Identification with Live-Cell Photoaffinity Labeling and Mechanism of Action Elucidation of ARN23765, a Highly Potent CFTR Corrector.Journal of medicinal chemistry · 2025Article
- Effect of CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor on lipid metabolism in human bronchial epithelial cells.Glycoconjugate journal · 2025Article
- Rescue of Mutant CFTR Channel Activity by Investigational Co-Potentiator Therapy.Biomedicines · 2025Article
- Article
- SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular ClSignal transduction and targeted therapy · 2024Article
- Structure-based discovery of CFTR potentiators and inhibitors.bioRxiv : the preprint server for biology · 2024Article
- SUMOylation Inhibition Enhances Protein Transcription under CMV Promoter: A Lesson from a Study with the F508del-CFTR Mutant.International journal of molecular sciences · 2024Article
- Specialized proresolving mediator resolvin E1 corrects the altered cystic fibrosis nasal epithelium cilia beating dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Laboratory Tools to Predict CFTR Modulator Therapy Effectiveness and to Monitor Disease Severity in Cystic Fibrosis.Journal of personalized medicine · 2024Review
- Innovative Strategy toward Mutant CFTR Rescue in Cystic Fibrosis: Design and Synthesis of Thiadiazole Inhibitors of the E3 Ligase RNF5.Journal of medicinal chemistry · 2023Article
- Clinical Consequences and Functional Impact of the Rare S737F CFTR Variant and Its Responsiveness to CFTR Modulators.International journal of molecular sciences · 2023Article
- SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation.Nature communications · 2023Article
- Phenotypic Alteration of an Established Human Airway Cell Line by Media Selection.International journal of molecular sciences · 2023Article
- Q1291H-CFTR molecular dynamics simulations andFrontiers in molecular biosciences · 2023Article
- Gain- and Loss-of-FunctionCells · 2022Article
- Article
- Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing.International journal of molecular sciences · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The F508del mutation, the most frequent in cystic fibrosis (CF), impairs the maturation of the CFTR chloride channel. The F508del defect can be partially overcome at low temperature (27°C) or with pharmacological correctors. However, the efficacy of correctors on the mutant protein appears to be dependent on the cell expression system. We have used a bronchial epithelial cell line, CFBE41o-, to determine the efficacy of various known treatments and to discover new correctors. Compared with other cell types, CFBE41o- shows the largest response to low temperature and the lowest one to correctors such as corr-4a and VRT-325. A screening of a small-molecule library identified 9-aminoacridine and ciclopirox, which were significantly more effective than corr-4a and VRT-325. Analysis with microarrays revealed that 9-aminoacridine, ciclopirox, and low temperature, in contrast to corr-4a, cause a profound change in cell transcriptome. These data suggest that 9-aminoacridine and ciclopirox act on F508del-CFTR maturation as proteostasis regulators, a mechanism already proposed for the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). However, we found that 9-aminoacridine, ciclopirox, and SAHA, in contrast to corr-4a, VRT-325, and low temperature, do not increase chloride secretion in primary bronchial epithelial cells from CF patients. These conflicting data appeared to be correlated with different gene expression signatures generated by these treatments in the cell line and in primary bronchial epithelial cells. Our results suggest that F508del-CFTR correctors acting by altering the cell transcriptome may be particularly active in heterologous expression systems but markedly less effective in native epithelial cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.