ArticleFrontiers in immunology2017
Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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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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
37 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- SECS, drugs, and Rac1&Rho: regulation of EnNaC in vascular endothelial cells.Pflugers Archiv : European journal of physiology · 2025Article
- The lectin-like domain of TNF reduces pneumonia-induced injury in the perfused human lung.JCI insight · 2025Article
- Can ENaC "TIP" the Scales to Reduce Endothelial Reactive Oxygen Species and Vascular Leak during Pneumococcal Lung Injury?American journal of respiratory cell and molecular biology · 2025Article
- Endothelial ENaC-α Restrains Oxidative Stress in Lung Capillaries in Murine Pneumococcal Pneumonia-associated Acute Lung Injury.American journal of respiratory cell and molecular biology · 2025Article
- Endothelial ENaC as a repressor of oxidative stress and a guardian of lung capillary barrier function in bacterial and viral pneumonia.Frontiers in physiology · 2025Review
- Editorial: Endocytic and trafficking events in acute lung injury and pulmonary inflammation.Frontiers in immunology · 2024Article
- Proteolytic Activation of the Epithelial Sodium Channel (ENaC): Its Mechanisms and Implications.International journal of molecular sciences · 2023Review
- The Epithelial Sodium Channel-An Underestimated Drug Target.International journal of molecular sciences · 2023Review
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Acute organ injury and long-term sequelae of severe pneumococcal infections.Pneumonia (Nathan Qld.) · 2023Review
- Acid-sensing ion channel 1a activates IKCa/SKCa channels and contributes to endothelium-dependent dilation.The Journal of general physiology · 2023Article
- Significance of Pulmonary Endothelial Injury and the Role of Cyclooxygenase-2 and Prostanoid Signaling.Bioengineering (Basel, Switzerland) · 2023Review
- Direct endothelial ENaC activation mitigates vasculopathy induced by SARS-CoV2 spike protein.Frontiers in immunology · 2023Article
- Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome.Respiratory research · 2022Review
- Responses to Ang II (Angiotensin II), Salt Intake, and Lipopolysaccharide Reveal the Diverse Actions of TNF-α (Tumor Necrosis Factor-α) on Blood Pressure and Renal Function.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Identifying the Molecular Mechanisms and Types of Cell Death Induced byInternational journal of molecular sciences · 2022Article
- Effects of amiloride on acetylcholine-dependent arterial vasodilation evolve over time in mice on a high salt diet.Physiological reports · 2022Article
- Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques.Journal of inflammation research · 2022Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
background
methodsThe presence of α, β, and γ subunits of ENaC and protein phosphorylation status in HL-MVEC were assessed in western blotting. The role of ENaC-α in monolayer resistance of HL-MVEC was examined by depletion of this subunit by specific siRNA and by employing the TNF-derived TIP peptide, a specific activator that directly binds to ENaC-α.
resultsHL-MVEC express all three subunits of ENaC, as well as acid-sensing ion channel 1a (ASIC1a), which has the capacity to form hybrid non-selective cation channels with ENaC-α. Both TIP peptide, which specifically binds to ENaC-α, and the specific ASIC1a activator MitTx significantly strengthened barrier function in PLY-treated HL-MVEC. ENaC-α depletion significantly increased sensitivity to PLY-induced hyperpermeability and in addition, blunted the protective effect of both the TIP peptide and MitTx, indicating an important role for ENaC-α and for hybrid NSC channels in barrier function of HL-MVEC. TIP peptide blunted PLY-induced phosphorylation of both calmodulin-dependent kinase II (CaMKII) and of its substrate, the actin-binding protein filamin A (FLN-A), requiring the expression of both ENaC-α and ASIC1a. Since non-phosphorylated FLN-A promotes ENaC channel open probability and blunts stress fiber formation, modulation of this activity represents an attractive target for the protective actions of ENaC-α in both barrier function and liquid clearance.
conclusionOur results in cultured endothelial cells demonstrate a previously unrecognized role for ENaC-α in strengthening capillary barrier function that may apply to the human lung. Strategies aiming to activate endothelial NSC channels that contain ENaC-α should be further investigated as a novel approach to improve barrier function in the capillary endothelium during pneumonia.
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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 Socratic graph.