ArticleAmerican journal of respiratory cell and molecular biology2017
Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.
Article in American journal of respiratory cell and molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Mechanotransducer Piezo1 drives ventilator‑induced lung injury in lung epithelial cells via the calcineurin/NFATc3 pathway.Molecular medicine reports · 2026Article
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Targeting IL6-Edn1-FoxO1 axis enables lung growth in mechanically ventilated newborn mice.The European respiratory journal · 2025Article
- MiR-27a-5p deficiency in plasma exosomes derived from obese individuals exacerbates ventilator-induced lung injury in vitro and in vivo.Journal of translational medicine · 2025Article
- Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model.International journal of molecular sciences · 2025Article
- Slow releasing sulphide donor GYY4137 protects mice against ventilator-induced lung injury.Intensive care medicine experimental · 2025Article
- Piezo1 and tissue fibrosis: insights into its role and potential for modulation.Burns & trauma · 2025Review
- Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.European journal of pediatrics · 2024Article
- Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration.Nature communications · 2023Article
- Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis.Journal of advanced research · 2023Article
- Mechanical Ventilation-Related High Stretch Mainly Induces Endoplasmic Reticulum Stress and Thus Mediates Inflammation Response in Cultured Human Primary Airway Smooth Muscle Cells.International journal of molecular sciences · 2023Article
- Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology.Frontiers in physiology · 2023Review
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress.Redox biology · 2022Article
- A tunable physiomimetic stretch system evaluated with precision cut lung slices and recellularized human lung scaffolds.Frontiers in bioengineering and biotechnology · 2022Article
- Molecular mechanisms of postintensive care syndrome.Intensive care medicine experimental · 2021Review
- Mathematical modeling of ventilator-induced lung inflammation.Journal of theoretical biology · 2021Article
- AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections.Scientific reports · 2021Article
- The integrated stress response in pulmonary disease.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Reduced Surfactant Contributes to Increased Lung Stiffness Induced by Rapid Inspiratory Flow.Lung · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.
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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.