ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
Role of MMP2 and MMP9 in TRPV4-induced lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 79 citations in OpenAlex.
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- NFAT5 Regulates IL8 to Promote Cell Growth and Migration in Non-Small Cell Lung Cancer.Thoracic cancer · 2025Article
- The Calcium Signalling Profile of the Inner Blood-Retinal Barrier in Diabetic Retinopathy.Cells · 2025Review
- Exploring Asthma Mechanism of Belamcanda Chinensis by "Dose-effect Weighted Coefficient" Network Pharmacology and Experiment Validation.Combinatorial chemistry & high throughput screening · 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
- Evaluation of GSK2789917-induced TRPV4 inhibition in animal models of fluid induced lung injury.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The endothelium: gatekeeper to lung ischemia-reperfusion injury.Respiratory research · 2024Review
- Article
- Impact of TRP Channels on Extracellular Matrix Remodeling: Focus on TRPV4 and Collagen.International journal of molecular sciences · 2024Review
- Gene Expression in Bronchial Epithelial Cell Responses to Vanadium Exposure.Biological trace element research · 2023Article
- Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel.International journal of chronic obstructive pulmonary disease · 2023Article
- Mechanosensitive channels in lung disease.Frontiers in physiology · 2023Review
- Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome.Respiratory research · 2022Review
- The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies.Acta pharmaceutica Sinica. B · 2022Review
- Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.Reviews of physiology, biochemistry and pharmacology · 2022Review
- TRPV4: Cell type-specific activation, regulation and function in the vertebrate eye.Current topics in membranes · 2022Article
- Role of the LRP1-pPyk2-MMP9 pathway in hyperoxia-induced lung injury in neonatal rats.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ca(2+) entry through transient receptor potential vanilloid 4 (TRPV4) results in swelling, blebbing, and detachment of the epithelium and capillary endothelium in the intact lung. Subsequently, increased permeability of the septal barrier and alveolar flooding ensue. In this study, we tested the hypothesis that TRPV4 activation provides a Ca(2+) source necessary for proteolytic disruption of cell-cell or cell-matrix adhesion by matrix metalloproteinases (MMPs) 2 and 9, thus increasing septal barrier permeability. In our study, C57BL/6 or TRPV4(-/-) mouse lungs were perfused with varying doses of the TRPV4 agonist GSK-1016790A (Sigma) and then prepared for Western blot. Lung injury, assessed by increases in lung wet-to-dry weight ratios and total protein levels in the bronchoalveolar lavage fluid, was increased in a dose-dependent fashion in TRPV4(+/+) but not TRPV4(-/-) lungs. In concert with lung injury, we detected increased active MMP2 and MMP9 isoforms, suggesting that TRPV4 can provide the Ca(2+) source necessary for increased MMP2/9 activation. Furthermore, tissue inhibitor of metalloproteinases (TIMP) 2 levels in the TRPV4-injured lungs were decreased, suggesting that TRPV4 activation increases the availability of these active MMPs. We then determined whether MMP2 and MMP9 mediate TRPV4-induced lung injury. Pharmacological blockade (SB-3CT, 1 μM; Sigma) of MMP2 and MMP9 resulted in protection against TRPV4-induced lung injury. We conclude that TRPV4 activation and the subsequent Ca(2+) transient initiates a rapid cascade of events leading to release and activation of the gelatinase MMPs, which then contribute to lung injury.
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