ArticleAmerican journal of respiratory cell and molecular biology2014
Role of claudin-5 in the attenuation of murine acute lung injury by simvastatin.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Claudin 5 Across the Vascular Landscape: From Blood-Tissue Barrier Regulation to Disease Mechanisms.Cells · 2025Review
- Increased Kindlin-2 via SMURF1 Inhibition Attenuates Endothelial Permeability and Acute Lung Injury.International journal of molecular sciences · 2025Article
- Secretome profiling of human epithelial cells exposed to cigarette smoke extract and their effect on human lung microvascular endothelial cells.Scientific reports · 2024Article
- SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression.Science advances · 2022Article
- Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury.Cell biochemistry and biophysics · 2021Review
- Article
- Role of Statins in Coronavirus-Related Disease (COVID-19): A Retrospective Cohort Study in Northern Italy.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2021Article
- UCHL1, a deubiquitinating enzyme, regulates lung endothelial cell permeability in vitro and in vivo.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Sphingosine Kinase 1 Plays an Important Role in Atorvastatin-Mediated Anti-Inflammatory Effect against Acute Lung Injury.Mediators of inflammation · 2021Article
- Gene Therapy for Acute Respiratory Distress Syndrome.Frontiers in physiology · 2021Review
- Targeting the blood-nerve barrier for the management of immune-mediated peripheral neuropathies.Experimental neurology · 2020Review
- Considerations for Statin Therapy in Patients with COVID-19.Pharmacotherapy · 2020Article
- Article
- The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard.Stem cell research & therapy · 2019Article
- Endothelial stromelysin1 regulation by the forkhead box-O transcription factors is crucial in the exudative phase of acute lung injury.Pharmacological research · 2019Article
- Current Understanding of Nasal Epithelial Cell Mis-Differentiation.Journal of inflammation research · 2019Review
- Attenuation of murine acute lung injury by PF-573,228, an inhibitor of focal adhesion kinase.Vascular pharmacology · 2018Article
- Impact of the Endothelial Tight Junction Protein Claudin-5 on Clinical Profiles of Patients With COPD.Allergy, asthma & immunology research · 2018Article
- TLR3 Regulated Poly I:C-Induced Neutrophil Extracellular Traps and Acute Lung Injury Partly Through p38 MAP Kinase.Frontiers in microbiology · 2018Article
- Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells.Journal of cellular physiology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The statins are now recognized to have pleiotropic properties, including augmentation of endothelial barrier function. To explore the mechanisms involved, we investigated the effect of simvastatin on endothelial cell (EC) tight junctions. Western blotting of human pulmonary artery ECs treated with simvastatin (5 μM) confirmed a significant time-dependent increase (16-48 h) in claudin-5 protein expression compared with controls, without detectable alterations in zonula occludens-1 or occludin. These effects were associated with membrane translocation of VE-cadherin, whereas translocation of vascular endothelial cadherin (VE-cadherin; silencing RNA) inhibited simvastatin-induced claudin-5 up-regulation. Moreover, simvastatin treatment of ECs induced increased phosphorylation of both FoxO1 and β-catenin, transcriptional regulators of claudin-5 expression mediated by VE-cadherin. Subsequently, we found no effect of claudin-5 silencing on EC barrier protection by simvastatin in response to thrombin stimulation, as measured by either transendothelial electrical resistance or by EC monolayer flux of FITC-dextran (2,000 kD). However, silencing of claudin-5 did significantly attenuate simvastatin-mediated EC barrier protection in response to thrombin, as measured by monolayer flux of sodium fluorescein (376 Da). Finally, employing a murine model of LPS-induced acute lung injury, there was no effect of claudin-5 silencing in vivo (intratracheal injection) on bronchoalveolar lavage fluid protein or cell counts, but LPS-induced lung tissue extravasation of the small molecular weight markers, sodium fluorescein and Hochst stain (562 Da), were significantly increased in claudin-5-silenced animals compared with simvastatin-treated control animals. These findings implicate a distinct mechanism underlying size-selective endothelial barrier-protective properties of statins, and may ultimately lead to new novel therapeutic targets for patients with acute lung injury.
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