ArticleThrombosis and haemostasis2019
Urokinase Plasminogen Activator Overexpression Reverses Established Lung Fibrosis.
Article in Thrombosis and haemostasis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Blood transcriptomic signatures distinguishEmerging microbes & infections · 2026Article
- Therapeutic Potential of Lentiviral miR-200a Mimics in Regulating Fibrinolysis and EMT Markers During Pulmonary Fibrosis.FASEB bioAdvances · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Review
- Serum profiling of uPA, PAI-1, and suPAR in systemic sclerosis: a preliminary study on analytical aspects and associations with microvascular and fibrotic manifestations.Frontiers in immunology · 2025Article
- The relationship between inflammatory factors and heart failure: evidence based on bidirectional Mendelian randomization analysis.Frontiers in cardiovascular medicine · 2024Article
- Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Inhibition of discoidin domain receptor 2 reveals kinase-dependent and kinase-independent functions in regulating fibroblast activity.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- The aged extracellular matrix and the profibrotic role of senescence-associated secretory phenotype.American journal of physiology. Cell physiology · 2023Review
- Article
- Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis.Communications biology · 2023Article
- The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19.Frontiers in immunology · 2023Article
- Functional Validation of the Putative Oncogenic Activity ofBiomedicines · 2022Article
- The uPA System Differentially Alters Fibroblast Fate and Profibrotic Ability in Skin Fibrosis.Frontiers in immunology · 2022Article
- The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review.International journal of molecular sciences · 2021Review
- Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts.Journal of cell science · 2020Article
- Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through αAmerican journal of respiratory cell and molecular biology · 2020Article
- You Say You Want a Resolution (of Fibrosis).American journal of respiratory cell and molecular biology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
introductionImpaired plasminogen activation (PA) is causally related to the development of lung fibrosis. Prior studies demonstrate that enhanced PA in the lung limits the severity of scarring following injury and in vitro studies indicate that PA promotes matrix degradation and fibroblast apoptosis. These findings led us to hypothesize that increased PA in an in vivo model would enhance the resolution of established lung fibrosis in conjunction with increased myofibroblast apoptosis.
methodsTransgenic C57BL/6 mice with doxycycline inducible lung-specific urokinase plasminogen activator (uPA) expression or littermate controls were treated (day 0) with bleomycin or saline. Doxycycline was initiated on days 1, 9, 14, or 21. Lung fibrosis, stiffness, apoptosis, epithelial barrier integrity, and inflammation were assessed.
resultsProtection from fibrosis with uPA upregulation from day 1 through day 28 was associated with reduced parenchymal stiffness as determined by atomic force microscopy. Initiation of uPA expression beginning in the late inflammatory or the early fibrotic phase reduced stiffness and fibrosis at day 28. Induction of uPA activity in mice with established fibrosis decreased lung collagen and lung stiffness while increasing myofibroblast apoptosis. Upregulation of uPA did not alter lung inflammation but was associated with improved epithelial cell homeostasis.
conclusionRestoring intrapulmonary PA activity diminishes lung fibrogenesis and enhances the resolution of established lung fibrosis. This PA-mediated resolution is associated with increased myofibroblast apoptosis and improved epithelial cell homeostasis. These studies support the potential capacity of the lung to resolve existing scar in murine models.
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