ArticleJCI insight2017
Zinc deficiency primes the lung for ventilator-induced injury.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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
35 citing papers in PubMed, 65 citations in OpenAlex.
- Epithelial SLC39A1 prevents acute lung injury through zinc-mediated transcriptional activation of autophagy in male mice.Nature communications · 2026Article
- Serum zinc level independently predicts need for inpatient intubation among patients hospitalized with COVID-19: A prospective observational study.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2026Observational
- New insights into the role of metallothioneins in obesity and diabetes.International journal of obesity (2005) · 2025Review
- Is the Concentration of Trace Elements Zinc, Selenium, Copper, Manganese, and Iron a Predictor of Clinical Outcomes in Critically Ill Trauma Patients?Biological trace element research · 2025Article
- What do we know about micronutrients in critically ill patients? A narrative review.JPEN. Journal of parenteral and enteral nutrition · 2025Review
- Dietary zinc deficiency promotes Acinetobacter baumannii lung infection via IL-13 in mice.Nature microbiology · 2024Article
- Article
- The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis.Antioxidants (Basel, Switzerland) · 2023Review
- Clinical nutrition approach in medical management of COVID-19 hospitalized patients: A narrative review.Nutrition and health · 2022Review
- The Role of Diet and Supplements in the Prevention and Progression of COVID-19: Current Knowledge and Open Issues.Preventive nutrition and food science · 2022Review
- The ZIP8/SIRT1 axis regulates alveolar progenitor cell renewal in aging and idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2022Article
- Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation.Biological trace element research · 2022Review
- The Role of Zinc in the Pathogenesis of Lung Disease.Nutrients · 2022Review
- Environmental-level exposure to metals and metal-mixtures associated with spirometry-defined lung disease in American Indian adults: Evidence from the Strong Heart Study.Environmental research · 2022Article
- "MATH+" Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale.Journal of clinical medicine research · 2022Review
- Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19.The British journal of nutrition · 2022Review
- Upper Airways Spray for Viral Infections Prevention.Journal of immunology research · 2022Observational
- Plasma zinc status and hyperinflammatory syndrome in hospitalized COVID-19 patients: An observational study.International immunopharmacology · 2021Observational
- Zinc supplementation as an adjunct therapy for COVID-19: Challenges and opportunities.British journal of clinical pharmacology · 2021Review
- The correlation between serum selenium, zinc, and COVID-19 severity: an observational study.BMC infectious diseases · 2021Observational
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Mechanical ventilation is necessary to support patients with acute lung injury, but also exacerbates injury through mechanical stress-activated signaling pathways. We show that stretch applied to cultured human cells, and to mouse lungs in vivo, induces robust expression of metallothionein, a potent antioxidant and cytoprotective molecule critical for cellular zinc homeostasis. Furthermore, genetic deficiency of murine metallothionein genes exacerbated lung injury caused by high tidal volume mechanical ventilation, identifying an adaptive role for these genes in limiting lung injury. Stretch induction of metallothionein required zinc and the zinc-binding transcription factor MTF1. We further show that mouse dietary zinc deficiency potentiates ventilator-induced lung injury, and that plasma zinc levels are significantly reduced in human patients who go on to develop acute respiratory distress syndrome (ARDS) compared with healthy and non-ARDS intensive care unit (ICU) controls, as well as with other ICU patients without ARDS. Taken together, our findings identify a potentially novel adaptive response of the lung to stretch and a critical role for zinc in defining the lung's tolerance for mechanical ventilation. These results demonstrate that failure of stretch-adaptive responses play an important role in exacerbating mechanical ventilator-induced lung injury, and identify zinc and metallothionein as targets for lung-protective interventions in patients requiring mechanical ventilation.
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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.