ArticleThe Journal of clinical investigation2013
Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review ofTheranostics · 2021Pooled it
- Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.Critical care (London, England) · 2022Trial
- Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial.Critical care (London, England) · 2020Trial
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
- Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- CRAC channels as targets for immunotherapy.Current opinion in immunology · 2026Review
- Nox1-Derived ROS Amplifies Calcium Entry and Enhances Pneumolysin-Induced Lung Endothelial Barrier Dysfunction in Hyperglycemia.Antioxidants (Basel, Switzerland) · 2026Article
- BTP2, a store-operated calcium channel inhibitor, attenuates morphine antinociceptive tolerance in rats.Frontiers in neuroscience · 2026Article
- STIM1 as an Early Predictive Biomarker for Acute Respiratory Distress Syndrome (ARDS) and Its Potential Mechanisms.Human mutation · 2026Article
- Inhibition of Calcium Release-Activated Calcium Channels to Treat Acute Kidney Injury: Design and Rationale of the KOURAGE Study a Randomized Trial.American journal of nephrology · 2026Article
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
- Review
- Glutamate Exacerbates Traumatic Brain Injury-Induced Acute Lung Injury Through NMDAR/ROS/CaThe Kaohsiung journal of medical sciences · 2025Article
- Endothelial Trauma Depends on Surface Charge and Extracellular Calcium Levels.bioRxiv : the preprint server for biology · 2025Article
- BTP2 restricts Tulane virus and human norovirus replication independent of store-operated calcium entry.Journal of virology · 2025Article
- The association between albumin corrected calcium levels and mortality in ICU patients undergoing maintenance hemodialysis.Scientific reports · 2025Article
- Addressing unexpected bacterial RNA safety concerns of E. coli produced influenza NP through CpG loaded mutant.NPJ vaccines · 2025Article
- Mechanism of CaMolecular biology reports · 2025Article
- Mac-1 blockade impedes adhesion-dependent neutrophil extracellular trap formation and ameliorates lung injury in LPS-induced sepsis.Frontiers in immunology · 2025Article
- Crosstalk Between Cell Death and the cGAS-STING Pathway in Sepsis-Associated Acute Lung Injury.Journal of inflammation research · 2025Review
76 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
During sepsis, acute lung injury (ALI) results from activation of innate immune cells and endothelial cells by endotoxins, leading to systemic inflammation through proinflammatory cytokine overproduction, oxidative stress, and intracellular Ca2+ overload. Despite considerable investigation, the underlying molecular mechanism(s) leading to LPS-induced ALI remain elusive. To determine whether stromal interaction molecule 1-dependent (STIM1-dependent) signaling drives endothelial dysfunction in response to LPS, we investigated oxidative and STIM1 signaling of EC-specific Stim1-knockout mice. Here we report that LPS-mediated Ca2+ oscillations are ablated in ECs deficient in Nox2, Stim1, and type II inositol triphosphate receptor (Itpr2). LPS-induced nuclear factor of activated T cells (NFAT) nuclear accumulation was abrogated by either antioxidant supplementation or Ca2+ chelation. Moreover, ECs lacking either Nox2 or Stim1 failed to trigger store-operated Ca2+ entry (SOCe) and NFAT nuclear accumulation. LPS-induced vascular permeability changes were reduced in EC-specific Stim1-/- mice, despite elevation of systemic cytokine levels. Additionally, inhibition of STIM1 signaling prevented receptor-interacting protein 3-dependent (RIP3-dependent) EC death. Remarkably, BTP2, a small-molecule calcium release-activated calcium (CRAC) channel blocker administered after insult, halted LPS-induced vascular leakage and pulmonary edema. These results indicate that ROS-driven Ca2+ signaling promotes vascular barrier dysfunction and that the SOCe machinery may provide crucial therapeutic targets to limit sepsis-induced ALI.
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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.