ArticleAutophagy2012
Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator.
Article in Autophagy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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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.
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Who cites it
59 citing papers in PubMed, 91 citations in OpenAlex.
- A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.Cell death and differentiation · 2016Trial
- Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.Autophagy · 2014Trial
- Host transcriptomic analysis reveals a defective intracellular environment that limits SARS-CoV-2 replication in CFTR-deficient airway epithelium.Frontiers in cellular and infection microbiology · 2026Article
- Article
- Effect of CFTR Modulators on Oxidative Stress and Autophagy in Non-CFTR-Expressing Cells.International journal of molecular sciences · 2024Article
- Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant "autophagy checkpoint".Aging cell · 2023Review
- Crosslink between SARS-CoV-2 replication and cystic fibrosis hallmarks.Frontiers in microbiology · 2023Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy.The Journal of clinical investigation · 2022Article
- CFTR Modulators Restore Acidification of Autophago-Lysosomes and Bacterial Clearance in Cystic Fibrosis Macrophages.Frontiers in cellular and infection microbiology · 2022Article
- Hepatocyte proteomes reveal the role of protein disulfide isomerase 4 in alpha 1-antitrypsin deficiency.JHEP reports : innovation in hepatology · 2021Article
- Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19.Frontiers in immunology · 2021Review
- Cystic Fibrosis Lung Disease in the Aging Population.Frontiers in pharmacology · 2021Review
- Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism.Cells · 2020Article
- CFTR Modulators DampenFrontiers in cellular and infection microbiology · 2020Article
- HDAC6 depletion improves cystic fibrosis mouse airway responses to bacterial challenge.Scientific reports · 2019Article
- Cystic fibrosis transmembrane conductance regulator (CFTR) and autophagy: hereditary defects in cystic fibrosisOncotarget · 2019Review
- Methylomic correlates of autophagy activity in cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2019Article
- Article
Corrections and comments
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Authors and funding
16 authors at 10 institutions in 5 countries.
Funding
Abstract
Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically unstable at the plasma membrane (PM) even if rescued by pharmacological correctors. We have demonstrated that human and mouse CF airways are autophagy deficient due to functional sequestration of BECN1 and that the tissue transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent autophagy and reduce SQSTM1/p62 levels, thus favoring ΔF508-CFTR trafficking to the epithelial surface. Here, we investigated whether these treatments could facilitate the beneficial action of potentiators on ΔF508-CFTR homozygous airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134 stabilized ΔF508-CFTR at the plasma membrane of airway epithelial cells and sustained the expression of CFTR at the epithelial surface well beyond drug withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the beneficial action of potentiators in controlling inflammation in ex vivo ΔF508-CFTR homozygous human nasal biopsies and in vivo in mouse ΔF508-CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in ΔF508-CFTR mice synergized with potentiators in sustaining surface CFTR expression and suppressing inflammation. Cystamine pre-treatment restored ΔF508-CFTR response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly isolated brushed nasal epithelial cells from ΔF508-CFTR homozygous patients. These findings delineate a novel therapeutic strategy for the treatment of CF patients with the ΔF508-CFTR mutation in which patients are first treated with cystamine and subsequently pulsed with CFTR potentiators.
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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.