ArticleTranslational research : the journal of laboratory and clinical medicine2021
Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.
Article in Translational research : the journal of laboratory and clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages.Biomolecules · 2026Article
- Neurocognitive Aging Following Acute Illness: Pathobiology and a Framework for Developing Neurotherapeutic Agents.Brain and behavior · 2026Review
- Progress on the mechanism of Piezo1 in mechanical ventilation-induced lung injury.Journal of thoracic disease · 2026Review
- Pulmonary Vascular Endothelial Cells in Lung Diseases: Mechanisms, Therapeutic Strategies, and Future Directions.Cell proliferation · 2026Review
- Developmentally Regulated CYP2E1 Expression Is Associated with a Fetal Pulmonary Transcriptional Response to Maternal Acetaminophen Exposure.Biomedicines · 2025Article
- Phenotype disruption of umbilical cord derived MSC by cyclic mechanical stretch and hyperoxia mediated by p21.Scientific reports · 2025Article
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- The context-dependent effect of cellular senescence: From embryogenesis and wound healing to aging.Ageing research reviews · 2025Review
- Analysis of Stratifin Expression and Proteome Variation in a Rat Model of Acute Lung Injury.Journal of proteome research · 2025Article
- Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies.Signal transduction and targeted therapy · 2025Review
- Mechanism of Shashen Maidong Decoction in the Treatment of Radiation Pneumonitis Based on Network Pharmacology and Molecular Docking.Current pharmaceutical design · 2025Article
- Article
- Senescence landscape in the liver following sepsis and senolytics as potential therapeutics.Aging cell · 2025Article
- RNA Sequencing Analysis of Monocytes Exposed to Airway Fluid From Children With Pediatric Acute Respiratory Distress Syndrome.Critical care explorations · 2024Article
- Article
- Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities.Annals of intensive care · 2024Review
- Expression of Angiopoietin-2 in Lung Tissue of Juvenile SD Rats with Lipopolysaccharide-Induced Acute Lung Injury and the Role of Ulinastatin.Archivum immunologiae et therapiae experimentalis · 2023Article
- Article
- Cellular Senescence in Acute and Chronic Wound Repair.Cold Spring Harbor perspectives in biology · 2022Review
- Stratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage.Nature communications · 2022Article
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
Abstract
The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir and/or ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an antiapoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence.
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