ArticleThe Journal of clinical investigation2010
The antifibrotic effects of plasminogen activation occur via prostaglandin E2 synthesis in humans and mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 143 citations in OpenAlex.
- Plasma Proteomic Signatures of Coagulopathy Following Traumatic Injury: Links to Biomechanics and Patient Outcomes.Shock (Augusta, Ga.) · 2026Article
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- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- COX-2/PGE₂ signaling drives Toxocara canis-induced lung pathology by enhancing plasminogen activator activity and collagen VI degradation.Scientific reports · 2025Article
- Exploring mechanisms of radiation-induced myocardial fibrosis using HMGB1 neutralizing antibody.Journal of molecular histology · 2025Article
- Pulmonary fibrosis: from mechanisms to therapies.Journal of translational medicine · 2025Review
- RNA-sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy.Physiological reports · 2024Article
- Metabolic alterations and mitochondrial dysfunction in human airway BEAS-2B cells exposed to vanadium pentoxide.Toxicology · 2024Article
- Prostaglandin EFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Crosstalk between the plasminogen/plasmin system and inflammation resolution.Journal of thrombosis and haemostasis : JTH · 2023Review
- Review
- Low-dose vanadium pentoxide perturbed lung metabolism associated with inflammation and fibrosis signaling in male animal and in vitro models.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
- Oncostatin M, Serpins, and Oxidative Stress in Extracellular Matrix Remodeling and Arteriovenous Fistula Maturation.Cardiology and cardiovascular medicine · 2023Article
- Myeloid- and Epithelial-derived Heparin-Binding Epidermal Growth Factor-like Growth Factor Promotes Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- PTPα promotes fibroproliferative responses after acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Lung Fibrosis and Fibrosis in the Lungs: Is It All about Myofibroblasts?Biomedicines · 2022Review
- Review
- α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis.Life (Basel, Switzerland) · 2022Review
- M2 macrophages have unique transcriptomes but conditioned media does not promote profibrotic responses in lung fibroblasts or alveolar epithelial cells in vitro.American journal of physiology. Lung cellular and molecular physiology · 2021Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Plasminogen activation to plasmin protects from lung fibrosis, but the mechanism underlying this antifibrotic effect remains unclear. We found that mice lacking plasminogen activation inhibitor-1 (PAI-1), which are protected from bleomycin-induced pulmonary fibrosis, exhibit lung overproduction of the antifibrotic lipid mediator prostaglandin E2 (PGE2). Plasminogen activation upregulated PGE2 synthesis in alveolar epithelial cells, lung fibroblasts, and lung fibrocytes from saline- and bleomycin-treated mice, as well as in normal fetal and adult primary human lung fibroblasts. This response was exaggerated in cells from Pai1-/- mice. Although enhanced PGE2 formation required the generation of plasmin, it was independent of proteinase-activated receptor 1 (PAR-1) and instead reflected proteolytic activation and release of HGF with subsequent induction of COX-2. That the HGF/COX-2/PGE2 axis mediates in vivo protection from fibrosis in Pai1-/- mice was demonstrated by experiments showing that a selective inhibitor of the HGF receptor c-Met increased lung collagen to WT levels while reducing COX-2 protein and PGE2 levels. Of clinical interest, fibroblasts from patients with idiopathic pulmonary fibrosis were found to be defective in their ability to induce COX-2 and, therefore, unable to upregulate PGE2 synthesis in response to plasmin or HGF. These studies demonstrate crosstalk between plasminogen activation and PGE2 generation in the lung and provide a mechanism for the well-known antifibrotic actions of the fibrinolytic pathway.
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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.