ArticleThe Journal of experimental medicine2012
TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 232 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
- Bidirectional crosstalk between TRP channels and Toll-like receptors in inflammation and host defense.Journal of neuroinflammation · 2026Review
- Condensation of cGAS induced by TyrScience signaling · 2026Article
- A Muribaculaceae-enriched microbiota exacerbates TLR4-dependent Acinetobacter baumannii-induced hyperinflammatory sepsis.Nature communications · 2026Article
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- ERG-deficient endothelium identifies IL-8/CXCR2 axis as a therapeutic target for resolving neutrophilic lung vascular injury.JCI insight · 2026Article
- TRPC6-Mediated CaCells · 2026Article
- Immune sentinel function of nasal mucosal epithelial cells in allergic rhinitis: a review on barrier damage and inflammatory amplification loops regulated by calcium signalling.Frontiers in immunology · 2026Review
- Bacterial vaginosis toxins impair sperm capacitation and fertilization.Human reproduction (Oxford, England) · 2025Article
- Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury.iScience · 2025Article
- Transient Receptor Potential Channels in Vascular Mechanotransduction.American journal of hypertension · 2025Review
- GLP-1/GLP-1R axis: from metabolism (obesity and T2DM) to immunity.Open biology · 2025Review
- Modulation of IRAK4 as a therapeutic strategy against monosodium urate- and xanthine-induced inflammation in macrophages and HepG2 cells.Frontiers in immunology · 2025Article
- Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.Medicinal research reviews · 2024Review
- FAK regulates tension transmission to the nucleus and endothelial transcriptome independent of kinase activity.Cell reports · 2024Article
- Neuroimmune recognition and regulation in the respiratory system.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
- PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer.Frontiers in pharmacology · 2024Article
- Resistin Induces Migration and Invasion in PC3 Prostate Cancer Cells: Role of Extracellular Vesicles.Life (Basel, Switzerland) · 2023Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Lung vascular endothelial barrier disruption and the accompanying inflammation are primary pathogenic features of acute lung injury (ALI); however, the basis for the development of both remains unclear. Studies have shown that activation of transient receptor potential canonical (TRPC) channels induces Ca(2+) entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca(2+) signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca(2+) entry in ECs in a TLR4-dependent manner. Moreover, deletion of TRPC6 renders mice resistant to endotoxin-induced barrier dysfunction and inflammation, and protects against sepsis-induced lethality. TRPC6 induces Ca(2+) entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca(2+) entry mediated by TRPC6, in turn, activates the nonmuscle myosin light chain kinase (MYLK), which not only increases lung vascular permeability but also serves as a scaffold to promote the interaction of myeloid differentiation factor 88 and IL-1R-associated kinase 4, which are required for NF-κB activation and lung inflammation. Our findings suggest that TRPC6-dependent Ca(2+) entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin.
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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.