ArticleProceedings of the National Academy of Sciences of the United States of America2013
Endothelial glucocorticoid receptor is required for protection against sepsis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
87 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Corticosteroids for treating sepsis in children and adults.The Cochrane database of systematic reviews · 2025Pooled it
- Corticosteroids for treating sepsis in children and adults.The Cochrane database of systematic reviews · 2019Pooled it
- Do low-dose corticosteroids improve survival or shock reversal from septic shock in adults? Meta-analysis with trial sequential analysis.The Journal of international medical research · 2018Pooled it
- Corticosteroids for treating sepsis.The Cochrane database of systematic reviews · 2015Pooled it
- Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial.Critical care (London, England) · 2017Trial
- Inter-Organ Communication Networks in Systemic Physiology: Glucocorticoid Receptor α as a Central Integrator of Homeostasis.International journal of molecular sciences · 2026Review
- Impact of Chronic Mild Stress on Neurotrophic and Hypothalamic-Pituitary-Adrenal Factors in the Brain of Rats Submitted to Sepsis.Neurotoxicity research · 2026Article
- Trajectories of mean arterial pressure/norepinephrine equivalent dose index in patients with septic shock receiving low-dose hydrocortisone: a retrospective cohort study in Thailand.Acute and critical care · 2026Article
- Activation of aryl hydrocarbon receptor signaling by indole-3-lactic acid from Bacillus velezensis DS2 reinforces gut mucosal immunity and attenuates inflammaging in aged mice.Immunity & ageing : I & A · 2025Article
- Corticosteroids in sepsis.Journal of intensive medicine · 2025Review
- HNF4A mitigates sepsis-associated lung injury by upregulating NCOR2/GR/STAB1 axis and promoting macrophage polarization towards M2 phenotype.Cell death & disease · 2025Article
- The Role of SR-BI in sepsis: leveraging mechanistic insights to advance precision steroid therapy.Frontiers in immunology · 2025Review
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- Corticosteroids in sepsis and community-acquired pneumonia.Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2023Review
- Loss of endothelial glucocorticoid receptor accelerates organ fibrosis inAmerican journal of physiology. Renal physiology · 2023Article
- Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling.International journal of molecular sciences · 2023Review
- Changes in Cortisol Secretion and Corticosteroid Receptors in COVID-19 and Non COVID-19 Critically Ill Patients with Sepsis/Septic Shock and Scope for Treatment.Biomedicines · 2023Review
- Corticosteroids in ARDS.Journal of clinical medicine · 2023Review
- Emerging concepts in the care of patients with cirrhosis and septic shock.World journal of hepatology · 2023Review
- Loss of endothelial glucocorticoid receptor accelerates organ fibrosis inbioRxiv : the preprint server for biology · 2023Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
The glucocorticoid receptor (GR) is ubiquitously expressed on nearly all cell types, but tissue-specific deletion of this receptor can produce dramatic whole organism phenotypes. In this study we investigated the role of the endothelial GR in sepsis in vivo and in vitro. Mice with an endothelial-specific GR deletion and controls were treated with 12.5 mg/kg LPS and phenotyped. Mice lacking GR showed significantly increased mortality, more hemodynamic instability, higher nitric oxide levels, and higher levels of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) compared with controls. There were no differences in rates of apoptosis or macrophage recruitment between the two groups. Both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression were increased after LPS challenge in mice with endothelial GR deficiency, and aminoguanidine, a specific iNOS inhibitor in mice was able to rescue hemodynamic collapse in these animals. In vitro, human umbilical vein cells (HUVECs) subjected to GR knockdown by siRNA showed increased expression of eNOS at baseline that persisted after treatment with LPS. Both eNOS and iNOS mRNA was increased by qPCR. In HUVECs lacking GR, NF-κB levels and NF-κB-dependent genes tissue factor and IL-6 were increased compared with controls. Thus, endothelial GR is a critical regulator of NF-κB activation and nitric oxide synthesis in sepsis.
Indexed as
Identifiers
What OpenQuestion holds
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.