ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 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.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- Biophysical and aerodynamic properties of a peptide targeting the A-kinase anchoring function of PI3Kγ for pulmonary cAMP modulation.Scientific reports · 2026Article
- Is the SPLUNC1-Orai1 axis a critical determinant of lung health?Biochemical Society transactions · 2025Review
- Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.Scientific reports · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Is developmental plasticity triggered by DNA methylation changes in the invasive cane toad (Ecology and evolution · 2024Article
- Lung SPLUNC1 Peptide Derivatives in the Lipid Membrane Headgroup Kill Gram-Negative Planktonic and Biofilm Bacteria.Biomacromolecules · 2023Article
- The postbiotic of hawthorn-probiotic ameliorating constipation caused by loperamide in elderly mice by regulating intestinal microecology.Frontiers in nutrition · 2023Article
- Preclinical evaluation of the epithelial sodium channel inhibitor AZD5634 and implications on human translation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Charting a New Path: A Single-Cell Atlas of Porcine Cystic Fibrosis Airways at Birth.American journal of respiratory cell and molecular biology · 2022Article
- Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- CFTR Protein: Not Just a Chloride Channel?Cells · 2021Review
- Review
- An Adverse Outcome Pathway for Decreased Lung Function Focusing on Mechanisms of Impaired Mucociliary Clearance Following Inhalation Exposure.Frontiers in toxicology · 2021Article
- Degradation of bacterial permeability family member A1 (BPIFA1) by house dust mite (HDM) cysteine protease Der p 1 abrogates immune modulator function.International journal of biological macromolecules · 2020Article
- The SPLUNC1-βENaC complex prevents Burkholderia cenocepacia invasion in normal airway epithelia.Respiratory research · 2020Article
- Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies.Pharmaceutics · 2020Review
- Cystic Fibrosis: Emergence of Highly Effective Targeted Therapeutics and Potential Clinical Implications.American journal of respiratory and critical care medicine · 2020Review
- Novel therapeutic approaches for the management of cystic fibrosis.Multidisciplinary respiratory medicine · 2020Article
- Selection in Australian Thoroughbred horses acts on a locus associated with early two-year old speed.PloS one · 2020Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The epithelial sodium channel (ENaC) is responsible for Na(+) and fluid absorption across colon, kidney, and airway epithelia. Short palate lung and nasal epithelial clone 1 (SPLUNC1) is a secreted, innate defense protein and an autocrine inhibitor of ENaC that is highly expressed in airway epithelia. While SPLUNC1 has a bactericidal permeability-increasing protein (BPI)-type structure, its NH2-terminal region lacks structure. Here we found that an 18 amino acid peptide, S18, which corresponded to residues G22-A39 of the SPLUNC1 NH2 terminus inhibited ENaC activity to a similar degree as full-length SPLUNC1 (∼2.5 fold), while SPLUNC1 protein lacking this region was without effect. S18 did not inhibit the structurally related acid-sensing ion channels, indicating specificity for ENaC. However, S18 preferentially bound to the βENaC subunit in a glycosylation-dependent manner. ENaC hyperactivity is contributory to cystic fibrosis (CF) lung disease. Unlike control, CF human bronchial epithelial cultures (HBECs) where airway surface liquid (ASL) height was abnormally low (4.2 ± 0.6 μm), addition of S18 prevented ENaC-led ASL hyperabsorption and maintained CF ASL height at 7.9 ± 0.6 μm, even in the presence of neutrophil elastase, which is comparable to heights seen in normal HBECs. Our data also indicate that the ENaC inhibitory domain of SPLUNC1 may be cleaved away from the main molecule by neutrophil elastase, suggesting that it may still be active during inflammation or neutrophilia. Furthermore, the robust inhibition of ENaC by the S18 peptide suggests that this peptide may be suitable for treating CF lung disease.
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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.