ArticlePloS one2016
Src Family Kinases Modulate the Loss of Endothelial Barrier Function in Response to TNF-α: Crosstalk with p38 Signaling.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Piezo1-Src signaling rapidly disrupts brain endothelial barrier integrity.Fluids and barriers of the CNS · 2026Article
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- Identification of oxidative phosphorylation-related genes in moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.Frontiers in genetics · 2024Article
- Determination of Endothelial Barrier Resistance by Electric Cell-Substrate Impedance Sensing (ECIS) System.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion.Frontiers in immunology · 2024Article
- Amphipathic Helical Peptide L37pA Protects against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor.American journal of respiratory cell and molecular biology · 2024Article
- Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.Clinical science (London, England : 1979) · 2023Review
- Pro-inflammatory role of Wnt/β-catenin signaling in endothelial dysfunction.Frontiers in cardiovascular medicine · 2022Article
- Apoptosis signal-regulating kinase 1 (ASK1) inhibition reduces endothelial cytokine production without improving permeability after toll-like receptor 4 (TLR4) challenge.Translational research : the journal of laboratory and clinical medicine · 2021Article
- Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin.eLife · 2020Article
- Identification of "antigen-specific" neutrophils in atherosclerosis patients that compromise vascular endothelial barrier function.American journal of translational research · 2020Article
- Integrin-dependent regulation of the endothelial barrier.Tissue barriers · 2019Review
- Ulinastatin Ameliorates Pulmonary Capillary Endothelial Permeability Induced by Sepsis Through Protection of Tight Junctions via Inhibition of TNF-α and Related Pathways.Frontiers in pharmacology · 2018Article
- Bushen Huoxue Attenuates Diabetes-Induced Cognitive Impairment by Improvement of Cerebral Microcirculation: Involvement of RhoA/ROCK/moesin and Src Signaling Pathways.Frontiers in physiology · 2018Article
- Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.Current pharmaceutical design · 2017Review
- Impaired activity of adherens junctions contributes to endothelial dilator dysfunction in ageing rat arteries.The Journal of physiology · 2017Article
- Regulation of endothelial barrier function by p120-catenin∙VE-cadherin interaction.Molecular biology of the cell · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Activation of Src Family Kinase (SFK) signaling is required for the increase in endothelial permeability induced by a variety of cytokines and growth factors. However, we previously demonstrated that activation of endogenous SFKs by expression of dominant negative C-terminal Src Kinase (DN-Csk) is not sufficient to decrease endothelial adherens junction integrity. Basal SFK activity has been observed in normal venular endothelia and was not associated with increased basal permeability. The basal SFK activity however was found to contribute to increased sensitivity of the venular endothelium to inflammatory mediator-induced leakage. How SFK activation achieves this is still not well understood. Here, we show that SFK activation renders human dermal microvascular endothelial cells susceptible to low doses of TNF-α. Treatment of DN-Csk-expressing cells with 50 pg/ml TNF-α induced a loss of TEER as well as drastic changes in the actin cytoskeleton and focal adhesion proteins. This synergistic effect was independent of ROCK or NF-κB activity. TNF-α-induced p38 signaling was required for the synergistic effect on barrier function, and activation of the p38 MAPK alone was also able to induce changes in permeability only in monolayers with active SFKs. These results suggest that the activation of endogenous levels of SFK renders the endothelial barrier more susceptible to low, physiologic doses of TNF-α through activation of p38 which leads to a loss of endothelial tight junctions.
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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.