ArticleAmerican journal of respiratory cell and molecular biology2014
Knockout mice reveal key roles for claudin 18 in alveolar barrier properties and fluid homeostasis.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Emerging roles of mechanosensitive ion channels in ventilator induced lung injury: a systematic review.Frontiers in immunology · 2024Pooled it
- Article
- Impaired Alveolar Barrier Integrity Exposes FGFR1 Orchestrating Tight Junction Homeostasis via Occludin Transcription Maintenance.International journal of biological sciences · 2026Article
- High-Altitude Hypoxic Preconditioning Attenuates Lipopolysaccharide-Induced Lung Injury and is Associated with Alveolar-Capillary Barrier Maintenance.Journal of inflammation research · 2026Article
- The role of Na,K‑ATPase in lung diseases (Review).Molecular medicine reports · 2025Review
- Correlation of CLDN18.2 and Tumor Microenvironment in Gastric Cancer: A Systematic Review.Cancers · 2025Review
- Biophysical basis of tight junction barrier modulation by a pan-claudin-binding molecule.PNAS nexus · 2025Article
- CAR-γδ T Cells Targeting Claudin18.2 Show Superior Cytotoxicity Against Solid Tumor Compared to Traditional CAR-αβ T Cells.Cancers · 2025Article
- BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.Autophagy reports · 2025Review
- Occludin Is Essential to Maintain Normal Alveolar Barrier Integrity and Its Protective Role During ARDS Progression.International journal of molecular sciences · 2024Article
- The preclinical discovery and development of zolbetuximab for the treatment of gastric cancer.Expert opinion on drug discovery · 2024Review
- Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications.Frontiers in oncology · 2023Review
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- New Insights into the Alveolar Epithelium as a Driver of Acute Respiratory Distress Syndrome.Biomolecules · 2022Review
- Stem cells, cell therapies, and bioengineering in lung biology and disease 2021.American journal of physiology. Lung cellular and molecular physiology · 2022Review
- Dysfunction of epithelial permeability barrier induced by HMGB1 in 2.5D cultures of human epithelial cells.Tissue barriers · 2022Review
- Local nebulization of 1α,25(OH)Respiratory research · 2022Article
- Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials.Tissue barriers · 2022Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJs) that regulate paracellular permeability to ions and solutes. Claudin 18, a member of the large claudin family, is highly expressed in lung alveolar epithelium. To elucidate the role of claudin 18 in alveolar epithelial barrier function, we generated claudin 18 knockout (C18 KO) mice. C18 KO mice exhibited increased solute permeability and alveolar fluid clearance (AFC) compared with wild-type control mice. Increased AFC in C18 KO mice was associated with increased β-adrenergic receptor signaling together with activation of cystic fibrosis transmembrane conductance regulator, higher epithelial sodium channel, and Na-K-ATPase (Na pump) activity and increased Na-K-ATPase β1 subunit expression. Consistent with in vivo findings, C18 KO alveolar epithelial cell (AEC) monolayers exhibited lower transepithelial electrical resistance and increased solute and ion permeability with unchanged ion selectivity. Claudin 3 and claudin 4 expression was markedly increased in C18 KO mice, whereas claudin 5 expression was unchanged and occludin significantly decreased. Microarray analysis revealed changes in cytoskeleton-associated gene expression in C18 KO mice, consistent with observed F-actin cytoskeletal rearrangement in AEC monolayers. These findings demonstrate a crucial nonredundant role for claudin 18 in the regulation of alveolar epithelial TJ composition and permeability properties. Increased AFC in C18 KO mice identifies a role for claudin 18 in alveolar fluid homeostasis beyond its direct contributions to barrier properties that may, at least in part, compensate for increased permeability.
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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.