ArticleProceedings of the National Academy of Sciences of the United States of America2011
Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 113 citations in OpenAlex.
- NEDD4L-mediated Gasdermin D and E ubiquitination regulates cell death and tissue injury.Cell death and differentiation · 2026Article
- E3 Ubiquitin Ligase Nedd4-2 Exacerbates Seizure-Induced Mitochondrial Defects in an Alzheimer's Disease Mouse Model.Journal of neurochemistry · 2026Article
- Transgenically expressed human delta epithelial sodium channel facilitated fluid absorption in mouse fetal lung explants.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Copy Number Variation in Asthma: An Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Longitudinal microcomputed tomography detects onset and progression of pulmonary fibrosis in conditionalAmerican journal of physiology. Lung cellular and molecular physiology · 2024Article
- The E3 ubiquitin ligase Nedd4L preserves skeletal muscle stem cell quiescence by inhibiting their activation.iScience · 2024Article
- Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity.The Journal of cell biology · 2024Article
- SCNN1B regulates the proliferation, migration, and collagen deposition of human lung fibroblasts.In vitro cellular & developmental biology. Animal · 2023Article
- Genome-Wide Acetylation Modification of H3K27ac in Bovine Rumen Cell Following Butyrate Exposure.Biomolecules · 2023Article
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Anti-apoptotic genes and non-coding RNAs are potential outcome predictors for ulcerative colitis.Functional & integrative genomics · 2023Article
- Involvement of miR-495 overexpression in the pathogenesis of bronchopulmonary dysplasia in preterm infants via the targeting ofAnnals of translational medicine · 2023Article
- Elevated intracellular NaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Association of cystic fibrosis transmembrane conductance regulator with epithelial sodium channel subunits carrying Liddle's syndrome mutations.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Linking Fibrotic Remodeling and Ultrastructural Alterations of Alveolar Epithelial Cells after Deletion ofInternational journal of molecular sciences · 2021Article
- Enhanced epithelial sodium channel activity in neonatal Scnn1b mouse lung attenuates high oxygen-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Congenital Deletion ofInternational journal of molecular sciences · 2021Article
- Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway.International journal of molecular sciences · 2021Review
- Osmotic Adaptation by NaBiomedicines · 2020Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Cystic fibrosis is caused by impaired ion transport due to mutated cystic fibrosis transmembrane conductance regulator, accompanied by elevated activity of the amiloride-sensitive epithelial Na(+) channel (ENaC). Here we show that knockout of the ubiquitin ligase Nedd4L (Nedd4-2) specifically in lung epithelia (surfactant protein C-expressing type II and Clara cells) causes cystic fibrosis-like lung disease, with airway mucus obstruction, goblet cell hyperplasia, massive inflammation, fibrosis, and death by three weeks of age. These effects of Nedd4L loss are likely caused by enhanced ENaC function, as reflected by increased ENaC protein levels, increased lung dryness at birth, amiloride-sensitive dehydration of lung explants, and elevated ENaC currents in primary alveolar type II cells analyzed by patch clamp recordings. Moreover, the lung defects were rescued with administration of amiloride into the lungs of young knockout pups via nasal instillation. Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia.
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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.