ArticleThe Journal of physiology2014
Cathepsin B contributes to Na+ hyperabsorption in cystic fibrosis airway epithelial cultures.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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
24 citing papers in PubMed, 39 citations in OpenAlex.
- Cathepsin B, Airway Pathogens, and Inflammation in the Lower Airways of Children With Cystic Fibrosis.Pediatric pulmonology · 2026Article
- Sex differences in airway disease: estrogen and airway surface liquid dynamics.Biology of sex differences · 2024Review
- Epithelial NaComprehensive Physiology · 2024Review
- Mycobacterium avium inhibits protein kinase C and MARCKS phosphorylation in human cystic fibrosis and non-cystic fibrosis cells.PloS one · 2024Article
- Proteolytic Activation of the Epithelial Sodium Channel (ENaC): Its Mechanisms and Implications.International journal of molecular sciences · 2023Review
- ENaC in Salt-Sensitive Hypertension: Kidney and Beyond.Current hypertension reports · 2020Review
- Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease.Human gene therapy · 2020Review
- Targeting Proteases in Cystic Fibrosis Lung Disease. Paradigms, Progress, and Potential.American journal of respiratory and critical care medicine · 2020Review
- Progress in Model Systems of Cystic Fibrosis Mucosal Inflammation to Understand Aberrant Neutrophil Activity.Frontiers in immunology · 2020Review
- Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020Review
- Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome.Journal of cellular and molecular medicine · 2019Article
- Cigarette Smoke Exposure Induces Retrograde Trafficking of CFTR to the Endoplasmic Reticulum.Scientific reports · 2019Article
- New insights regarding epithelial Na+ channel regulation and its role in the kidney, immune system and vasculature.Current opinion in nephrology and hypertension · 2019Review
- SPLUNC1 degradation by the cystic fibrosis mucosal environment drives airway surface liquid dehydration.The European respiratory journal · 2018Article
- CrossTalk proposal: mucosal acidification drives early progressive lung disease in cystic fibrosis.The Journal of physiology · 2018Article
- Epithelial NaAnnual review of physiology · 2018Review
- Esomeprazole Increases Airway Surface Liquid pH in Primary Cystic Fibrosis Epithelial Cells.Frontiers in pharmacology · 2018Article
- The Epithelial Sodium Channel Is a Modifier of the Long-Term Nonprogressive Phenotype Associated with F508del CFTR Mutations.American journal of respiratory cell and molecular biology · 2017Article
- Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span.The Journal of experimental medicine · 2017Article
- Chronic cathepsin inhibition by E-64 in Dahl salt-sensitive rats.Physiological reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In cystic fibrosis (CF) lung disease, the absence of functional CF transmembrane conductance regulator results in Cl(-)/HCO3 (-) hyposecretion and triggers Na(+) hyperabsorption through the epithelial Na(+) channel (ENaC), which contribute to reduced airway surface liquid (ASL) pH and volume. Prostasin, a membrane-anchored serine protease with trypsin-like substrate specificity has previously been shown to activate ENaC in CF airways. However, prostasin is typically inactive below pH 7.0, suggesting that it may be less relevant in acidic CF airways. Cathepsin B (CTSB) is present in both normal and CF epithelia and is secreted into ASL, but little is known about its function in the airways. We hypothesized that the acidic ASL seen in CF airways may stimulate CTSB to activate ENaC, contributing to Na(+) hyperabsorption and depletion of CF ASL volume. In Xenopus laevis oocytes, CTSB triggered α- and γENaC cleavage and induced an increase in ENaC activity. In bronchial epithelia from both normal and CF donor lungs, CTSB localized to the apical membrane. In normal and CF human bronchial epithelial cultures, CTSB was detected at the apical plasma membrane and in the ASL. CTSB activity was significantly elevated in acidic ASL, which correlated with increased abundance of ENaC in the plasma membrane and a reduction in ASL volume. This acid/CTSB-dependent activation of ENaC was ameliorated with the cell impermeable, CTSB-selective inhibitor CA074, suggesting that CTSB inhibition may have therapeutic relevance. Taken together, our data suggest that CTSB is a pathophysiologically relevant protease that activates ENaC in CF airways.
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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.