ArticleBlood2013
A critical role for Lyn kinase in strengthening endothelial integrity and barrier function.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 72 citations in OpenAlex.
- Discovery of potent kinase inhibitors with improved pharmacokinetics and safety potentials through structural optimization of dasatinib.Communications medicine · 2026Article
- LYN mutations in breast cancer: hypothesis-generating evidence for an association with central nervous system metastasis and domain-level insights.BMC cancer · 2025Article
- Plasma proteomics uncovers divergent molecular signatures in ischemic stroke and intracerebral hemorrhage.Biomarker research · 2025Article
- Hantaan virus activates Src family kinase and induces endothelial cell hyperpermeability via the TLR4/TRAF6 pathway.Journal of medical microbiology · 2025Article
- Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure.Cell reports · 2025Article
- CIRP contributes to multiple organ damage in acute pancreatitis by increasing endothelial permeability.Communications biology · 2025Article
- Interrogating endothelial barrier regulation by temporally resolved kinase network generation.Life science alliance · 2024Article
- The BulkECexplorer compiles endothelial bulk transcriptomes to predict functional versus leaky transcription.Nature cardiovascular research · 2024Article
- The dualistic role of Lyn tyrosine kinase in immune cell signaling: implications for systemic lupus erythematosus.Frontiers in immunology · 2024Review
- Ruscogenin ameliorates dasatinib-induced intestinal barrier dysfunction via ErbB4/YAP and ROCK/MLC pathways.Journal of natural medicines · 2023Article
- "Lyn"king Emphysema and Cancer Development: Insights from Src Family Kinase Gain-of-Function Models.American journal of respiratory cell and molecular biology · 2023Article
- Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.Nature communications · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells.International journal of molecular sciences · 2022Article
- Vascular Permeability in Diseases.International journal of molecular sciences · 2022Review
- Arenaviral infection causes bleeding in mice due to reduced serotonin release from platelets.Science signaling · 2022Article
- CD8+T Cell-Related Gene Biomarkers in Macular Edema of Diabetic Retinopathy.Frontiers in endocrinology · 2022Article
- Exploiting polypharmacology to dissect host kinases and kinase inhibitors that modulate endothelial barrier integrity.Cell chemical biology · 2021Article
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Neuropilin 1 Regulation of Vascular Permeability Signaling.Biomolecules · 2021Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The Src family kinases (SFKs) c-Src and Yes mediate vascular leakage in response to various stimuli including lipopolysaccharide (LPS) and vascular endothelial growth factor (VEGF). Here, we define an opposing function of another SFK, Lyn, which in contrast to other SFKs, strengthens endothelial junctions and thereby restrains the increase in vascular permeability. Mice lacking Lyn displayed increased mortality in LPS-induced endotoxemia and increased vascular permeability in response to LPS or VEGF challenge compared with wild-type littermates. Lyn knockout mice repopulated with wild-type bone marrow-derived cells have higher vascular permeability than wild-type mice, suggesting a role of endothelial Lyn in the maintenance of the vascular barrier. Small interfering RNA-mediated down-regulation of Lyn disrupted endothelial barrier integrity, whereas expression of a constitutively active mutant of Lyn enhanced the barrier. However, down-regulation of Lyn did not affect LPS-induced endothelial permeability. We demonstrate that Lyn association with focal adhesion kinase (FAK) and phosphorylation of FAK at tyrosine residues 576/577 and 925 were required for Lyn-dependent stabilization of endothelial adherens junctions. Thus, in contrast to c-Src and Yes, which increase vascular permeability in response to stimuli, Lyn stabilizes endothelial junctions through phosphorylation of FAK. Therefore, therapeutics activating Lyn kinase may strengthen the endothelial barrier junction and hence have anti-inflammatory potential.
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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.