ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Transient receptor potential channel 1 maintains adherens junction plasticity by suppressing sphingosine kinase 1 expression to induce endothelial hyperpermeability.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Sepsis-associated acute lung injury: do inflammatory lipid mediators flood the lungs by activating pulmonary TRP channels?Intensive care medicine experimental · 2026Review
- Elevated hydrostatic pressure destabilizes VE-cadherin junctions in a time and shear stress dependent manner: An endothelium-on-chip study.APL bioengineering · 2025Article
- Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome.Respiratory research · 2022Review
- Calcium-Permeable Channels and Endothelial Dysfunction in Acute Lung Injury.Current issues in molecular biology · 2022Review
- A narrative review of changes in microvascular permeability after burn.Annals of translational medicine · 2021Review
- Noncanonical function of long myosin light chain kinase in increasing ER-PM junctions and augmentation of SOCE.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Endothelial Cell Calcium Signaling during Barrier Function and Inflammation.The American journal of pathology · 2020Review
- Regulation of Vessel Permeability by TRP Channels.Frontiers in physiology · 2020Review
- Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling.Comprehensive Physiology · 2019Review
- Canonical Transient Receptor Potential Channels and Their Link with Cardio/Cerebro-Vascular Diseases.Biomolecules & therapeutics · 2017Review
- Roles of transient receptor potential channels in regulation of vascular and epithelial barriers.Tissue barriers · 2017Article
- Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability.Circulation research · 2017Review
- VE-cadherin complex plasticity: EPS8 and YAP play relay at adherens junctions.Tissue barriers · 2016Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Stability of endothelial cell (EC) adherens junctions (AJs) is central for prevention of tissue edema, the hallmark of chronic inflammatory diseases including acute respiratory distress syndrome. Here, we demonstrate a previously unsuspected role of sphingosine kinase 1 (SPHK1) in the mechanism by which transient receptor potential channel 1 (Trpc1)-mediated Ca(2+) entry destabilizes AJs. Trpc1(-/-) monolayers showed a 2.2-fold increase in vascular endothelial (VE)-cadherin cell-surface expression above wild-type (WT) monolayers. Thrombin increased endothelial permeability (evident by a 5-fold increase in interendothelial gap area and 60% decrease in transendothelial electrical resistance) in WT but not Trpc1(-/-) ECs. Trpc1(-/-) mice resisted the hyperpermeability effects of the edemagenic agonists used and exhibited 60% less endotoxin-induced mortality. Because sphingosine-1-phosphate (S1P) strengthens AJs, we determined if TRPC1 functioned by inhibiting SPHK1 activity, which generates S1P. Intriguingly, Trpc1(-/-) ECs or ECs transducing a TRPC1-inactive mutant showed a 1.5-fold increase in basal SPHK1 expression compared with WT ECs, resulting in a 2-fold higher S1P level. SPHK1 inhibitor SK1-I decreased basal transendothelial electrical resistance more in WT ECs (48 and 72% reduction at 20 and 50 μM, respectively) than in Trpc1(-/-) ECs. However, SK1-I pretreatment rescued thrombin-induced EC permeability in Trpc1(-/-) ECs. Thus, TRPC1 suppression of basal SPHK1 activity enables EC-barrier destabilization by edemagenic agonists.
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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.