ArticlePloS one2014
Tgf-beta downregulation of distinct chloride channels in cystic fibrosis-affected epithelia.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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.
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Who cites it
51 citing papers in PubMed, 93 citations in OpenAlex.
- Antifibrotic Drugs Regulate the Expression of Epithelial Sodium Channels in the Lungs.Advances in respiratory medicine · 2026Article
- Oral losartan yields subtherapeutic airway exposure compared to nebulized delivery and fails to improve mucociliary clearance in cystic fibrosis.Frontiers in pharmacology · 2026Article
- TGF-β induces excessive pulmonary IL-6 secretion in cystic fibrosis via PI3K.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Diagnosis and Emerging Biomarkers of Cystic Fibrosis-Related Kidney Disease (CFKD).Journal of clinical medicine · 2025Review
- Therapeutic strategies to reverse cigarette smoke-induced ion channel and mucociliary dysfunction in COPD airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- LMTK2 switches on canonical TGF-β1 signaling in human bronchial epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- MicroRNA mediated suppression of airway lactoperoxidase by TGF-β1 and cigarette smoke promotes airway inflammation.Journal of inflammation (London, England) · 2024Article
- Cystic fibrosis.Nature reviews. Disease primers · 2024Review
- Disrupting the TGF-β-Wnt Balance to Control the Polarity of the Cystic Fibrosis Airway Epithelium.American journal of respiratory cell and molecular biology · 2024Article
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond.The European respiratory journal · 2023Review
- Non-Coding RNAs in Pulmonary Diseases: Comparison of Different Airway-Derived Biosamples.International journal of molecular sciences · 2023Review
- Phenotypic Alteration of an Established Human Airway Cell Line by Media Selection.International journal of molecular sciences · 2023Article
- The CFTR Amplifier Nesolicaftor Rescues TGF-β1 Inhibition of Modulator-Corrected F508del CFTR Function.International journal of molecular sciences · 2022Article
- SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular ClSignal transduction and targeted therapy · 2022Article
- Losartan ameliorates TGF-β1-induced CFTR dysfunction and improves correction by cystic fibrosis modulator therapies.The Journal of clinical investigation · 2022Article
- Activation ofAmerican journal of physiology. Cell physiology · 2021Article
- Nasal Epithelial Cell-Based Models for Individualized Study in Cystic Fibrosis.International journal of molecular sciences · 2021Review
- Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Review
- The Prognostic Value and Mechanisms of TMEM16A in Human Cancer.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
rationaleThe cystic fibrosis transmembrane conductance regulator (CFTR) and Calcium-activated Chloride Conductance (CaCC) each play critical roles in maintaining normal hydration of epithelial surfaces including the airways and colon. TGF-beta is a genetic modifier of cystic fibrosis (CF), but how it influences the CF phenotype is not understood.
objectivesWe tested the hypothesis that TGF-beta potently downregulates chloride-channel function and expression in two CF-affected epithelia (T84 colonocytes and primary human airway epithelia) compared with proteins known to be regulated by TGF-beta. MEASUREMENTS AND MAIN
resultsTGF-beta reduced CaCC and CFTR-dependent chloride currents in both epithelia accompanied by reduced levels of TMEM16A and CFTR protein and transcripts. TGF-beta treatment disrupted normal regulation of airway-surface liquid volume in polarized primary human airway epithelia, and reversed F508del CFTR correction produced by VX-809. TGF-beta effects on the expression and activity of TMEM16A, wtCFTR and corrected F508del CFTR were seen at 10-fold lower concentrations relative to TGF-beta effects on e-cadherin (epithelial marker) and vimentin (mesenchymal marker) expression. TGF-beta downregulation of TMEM16A and CFTR expression were partially reversed by Smad3 and p38 MAPK inhibition, respectively.
conclusionsTGF-beta is sufficient to downregulate two critical chloride transporters in two CF-affected tissues that precedes expression changes of two distinct TGF-beta regulated proteins. Our results provide a plausible mechanism for CF-disease modification by TGF-beta through effects on CaCC.
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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.