ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Hydrogen peroxide-induced calcium influx in lung microvascular endothelial cells involves TRPV4.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 103 citations in OpenAlex.
- The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation.International journal of molecular sciences · 2026Review
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Are You a Friend or an Enemy? The Dual Action of Methylglyoxal on Brain Microvascular Endothelial Cells.International journal of molecular sciences · 2025Article
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- TRPV4 Mediates Alveolar Epithelial Barrier Integrity and Induces ADAM10-Driven E-Cadherin Shedding.Cells · 2024Article
- Study of the Synchronization and Transmission of Intracellular Signaling Oscillations in Cells Using Bispectral Analysis.Biology · 2024Article
- The endothelium: gatekeeper to lung ischemia-reperfusion injury.Respiratory research · 2024Review
- TRPV4 Activation and its Intracellular Modulation Mediated by Kinin Receptors Contribute to Painful Symptoms Induced by Anastrozole.Molecular neurobiology · 2024Article
- Fatty acid metabolism promotes TRPV4 activity in lung microvascular endothelial cells in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Article
- Reduction of TRPC1/TRPC3 mediated CaCellular signalling · 2023Article
- Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells.Cells · 2023Review
- Transpulmonary amino acid metabolism in the sugen hypoxia model of pulmonary hypertension.Pulmonary circulation · 2023Article
- Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome.Respiratory research · 2022Review
- Small molecule compound M12 reduces vascular permeability in obese mice via blocking endothelial TRPV4-Nox2 interaction.Acta pharmacologica Sinica · 2022Article
- Skin Microhemodynamics and Mechanisms of Its Regulation in Type 2 Diabetes Mellitus.Biophysics · 2022Article
- Endothelial TRPV4 channels in lung edema and injury.Current topics in membranes · 2022Review
- Leveraging avidin-biotin interaction to quantify permeability property of microvessels-on-a-chip networks.American journal of physiology. Heart and circulatory physiology · 2022Article
- Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Aging-Induced Impairment of Vascular Function: Mitochondrial Redox Contributions and Physiological/Clinical Implications.Antioxidants & redox signaling · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In acute respiratory distress syndrome, both reactive oxygen species (ROS) and increased intracellular calcium ([Ca(2+)]i) are thought to play important roles in promoting endothelial paracellular permeability, but the mechanisms linking ROS and [Ca(2+)]i in microvascular endothelial cells are not known. In this study, we assessed the effect of hydrogen peroxide (H2O2) on [Ca(2+)]i in mouse and human lung microvascular endothelial cells (MLMVEC and HLMVEC, respectively). We found that in both MLMVECs and HLMVECs, exogenously applied H2O2 increased [Ca(2+)]i through Ca(2+) influx and that pharmacologic inhibition of the calcium channel transient receptor potential vanilloid 4 (TRPV4) attenuated the H2O2-induced Ca(2+) influx. Additionally, knockdown of TRPV4 in HLMVEC also attenuated calcium influx following H2O2 challenge. Administration of H2O2 or TRPV4 agonists decreased transmembrane electrical resistance (TER), suggesting increased barrier permeability. To explore the regulatory mechanisms underlying TRPV4 activation by ROS, we examined H2O2-induced Ca(2+) influx in MLMVECs and HLMVECs with either genetic deletion, silencing, or pharmacologic inhibition of Fyn, a Src family kinase. In both MLMVECs derived from mice deficient for Fyn and HLMVECs treated with either siRNA targeted to Fyn or the Src family kinase inhibitor SU-6656 for 24 or 48 h, the H2O2-induced Ca(2+) influx was attenuated. Treatment with SU-6656 decreased the levels of phosphorylated, but not total, TRPV4 protein and had no effect on TRPV4 response to the external agonist, GSK1016790A. In conclusion, our data suggest that application of exogenous H2O2 increases [Ca(2+)]i and decreases TER in microvascular endothelial cells via activation of TRPV4 through a mechanism that requires the Src kinase Fyn.
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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.