ArticleAmerican journal of respiratory and critical care medicine2007
Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice.
Article in American journal of respiratory and critical care medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.American journal of respiratory cell and molecular biology · 2017Pooled it
- Pooled it
- A Premature Rabbit Kitten Model for Evaluation of Bronchopulmonary Dysplasia Therapies Reproduces Myeloperoxidase-Associated Pathology and Therapeutic Responses.International journal of molecular sciences · 2026Article
- Prediction of lung overdistension during mechanical ventilation using micro-RNA and gene expression.Intensive care medicine experimental · 2025Article
- Dynamic activity in cis-regulatory elements of leukocytes identifies transcription factor activation and stratifies COVID-19 severity in ICU patients.Cell reports. Medicine · 2023Article
- TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Pathogenesis of ventilator-induced lung injury: metabolomics analysis of the lung and plasma.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment-From Mice to Men.Biomedicines · 2022Review
- Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques.Journal of inflammation research · 2022Review
- Profiling Transcription Initiation in Peripheral Leukocytes Reveals Severity-Associated Cis-Regulatory Elements in Critical COVID-19.bioRxiv : the preprint server for biology · 2021Article
- Nrf2 Regulates Anti-InflammatoryAntioxidants (Basel, Switzerland) · 2021Article
- Protective function of DJ-1/PARK7 in lipopolysaccharide and ventilator-induced acute lung injury.Redox biology · 2021Article
- Preconditioning the immature lung with enhanced Nrf2 activity protects against oxidant-induced hypoalveolarization in mice.Scientific reports · 2020Article
- Novel drug delivery systems targeting oxidative stress in chronic obstructive pulmonary disease: a review.Journal of nanobiotechnology · 2020Review
- Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway.Frontiers in cell and developmental biology · 2020Article
- Upregulation of sphingosine kinase 1 contributes to ventilator-associated lung injury in a two-hit model.International journal of molecular medicine · 2019Article
- Article
- Human Adipose Tissue-Derived Stromal Cells Attenuate the Multiple Organ Injuries Induced by Sepsis and Mechanical Ventilation in Mice.Inflammation · 2019Article
- RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Pulmonary Effects of Adjusting Tidal Volume to Actual or Ideal Body Weight in Ventilated Obese Mice.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleMechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear.
objectivesWe hypothesized that disruption of the gene encoding Nrf2, a transcription factor that regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI) and that antioxidant supplementation attenuates this effect.
methodsTo test our hypothesis and to examine the relevance of oxidative stress in VILI, we assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) mice after an acute (2-h) injurious model of MV with or without administration of antioxidant. MEASUREMENTS AND MAIN
resultsNrf2(-/-) mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared with Nrf2(+/+) mice. Nrf2 deficiency enhances the levels of several proinflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2(-/-) mice; however, antioxidant supplementation to Nrf2(-/-) mice remarkably attenuated VILI. When subjected to a clinically relevant prolong period of MV, Nrf2(-/-) mice displayed greater levels of VILI than Nrf2(+/+) mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins, and phosphatases in Nrf2(-/-) mice.
conclusionsOur data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress.
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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.