ArticleThe American journal of pathology2004
The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis?The international journal of biochemistry & cell biology · 2008Pooled it
- Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2015Trial
- Targeted DNA triplex-forming oligonucleotide liposome for pulmonary fibrosis gene therapy.Cell reports. Medicine · 2026Article
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis.Life (Basel, Switzerland) · 2022Review
- Antifibrotic therapy by sustained release of low molecular weight heparin from poly(lactic-co-glycolic acid) microparticles on bleomycin-induced pulmonary fibrosis in mice.Scientific reports · 2020Article
- Alternatively activated macrophages are associated with the α2AP production that occurs with the development of dermal fibrosis : The role of alternatively activated macrophages on the development of fibrosis.Arthritis research & therapy · 2020Article
- Urokinase Plasminogen Activator Overexpression Reverses Established Lung Fibrosis.Thrombosis and haemostasis · 2019Article
- Chemical pleurodesis - a review of mechanisms involved in pleural space obliteration.Respiratory research · 2019Review
- Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development.Molecular therapy. Nucleic acids · 2017Article
- The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF.Scientific reports · 2017Article
- Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells.International journal of molecular sciences · 2016Article
- Libby amphibole-induced mesothelial cell autoantibodies bind to surface plasminogen and alter collagen matrix remodeling.Physiological reports · 2016Article
- Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease.Scientific reports · 2016Article
- Pleural mesothelial cells in pleural and lung diseases.Journal of thoracic disease · 2015Review
- Pathogenesis of Systemic Sclerosis.Frontiers in immunology · 2015Review
- Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2013Review
- Multiplex protein profiling of bronchoalveolar lavage in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis.Annals of thoracic medicine · 2013Article
- Developmental regulation of inflammatory cytokine-mediated Stat3 signaling: the missing link between intrauterine growth restriction and pulmonary dysfunction?Journal of molecular medicine (Berlin, Germany) · 2012Article
- SARS-CoV regulates immune function-related gene expression in human monocytic cells.Viral immunology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.
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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.