ArticleJCI insight2021
mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Mechanosensing at the endoplasmic reticulum by IRE1.Research square · 2026Article
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Revisiting ventilator-induced lung injury: from mechanical power to immunometabolic interaction.Frontiers in immunology · 2026Review
- The crosstalk between autophagy and ferroptosis in pulmonary fibrosis.Journal of biomedical research · 2025Article
- Microcystin-LR aerosol exposure increases inflammatory drivers of asthma, Evidence of an NF-κB amplification mechanism.bioRxiv : the preprint server for biology · 2025Article
- Aerosolized Harmful Algal Bloom Toxin Microcystin-LR Induces Type 1/Type 17 Inflammation of Murine Airways.Toxins · 2024Article
- A micro-scale humanized ventilator-on-a-chip to examine the injurious effects of mechanical ventilation.Lab on a chip · 2024Article
- Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- The effect of adoptive transferring myeloid-derived suppressor cells in ventilator-induced lung injury mice.Heliyon · 2024Article
- Association between serum high-density lipoprotein cholesterol and lung function in adults: three cross-sectional studies from US and Korea National Health and Nutrition Examination Survey.BMJ open respiratory research · 2023Article
- Article
- Review
- New Insights into the Alveolar Epithelium as a Driver of Acute Respiratory Distress Syndrome.Biomolecules · 2022Review
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
The acute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation (MV) maintains gas exchange in patients with ARDS but exposes lung cells to physical forces that exacerbate injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during MV impairs lung function. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion of Tsc2, a negative regulator of mTORC1, in epithelial cells impairs lung compliance during MV. Conversely, treatment with rapamycin at the time MV is initiated improves lung compliance without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during MV. Our data demonstrate that, in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during MV exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator-induced lung injury during ARDS.
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Registered trials
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