ArticleJCI insight2017
Uncoupling of the profibrotic and hemostatic effects of thrombin in lung fibrosis.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Targeting thrombin with hirudin alleviates paraquat-induced pulmonary fibrosis via the PAR-1-mediated TGF-β1 pathway.Histology and histopathology · 2026Article
- Peptide Angio-3 Attenuates Pulmonary Fibrosis Via Modulation of the Coagulation Factor Xa-Protease-Activated Receptor-1 Signaling Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Fibrotic Disease: from Signaling Pathways and Biomarkers to Molecular Imaging.Molecular imaging and biology · 2025Review
- Biological Aging and Uterine Fibrosis in Cattle: Reproductive Trade-Offs from Enhanced Productivity.Cells · 2025Review
- Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities.Biomolecules & biomedicine · 2025Review
- Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration.Cellular & molecular biology letters · 2025Review
- Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis.Expert reviews in molecular medicine · 2024Review
- Identifying prothrombin and bone sialoprotein as potential drug targets for idiopathic pulmonary fibrosis.BMC pulmonary medicine · 2024Article
- Fibrin-Positron Emission Tomography Imaging Reveals Ongoing Lung Injury in Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2024Article
- Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.International journal of molecular sciences · 2024Review
- Dosimetry of [medRxiv : the preprint server for health sciences · 2024Article
- Characterization of Biomarkers of Thrombo-Inflammation in Patients with First-Diagnosed Atrial Fibrillation.International journal of molecular sciences · 2024Article
- Unveiling the Role of PAR 1: A Crucial Link with Inflammation in Diabetic Subjects with COVID-19.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Role of platelet factor 4 in arteriovenous fistula maturation failure: What do we know so far?The journal of vascular access · 2024Review
- Molecular Imaging of Fibrosis in Benign Diseases: An Overview of the State of the Art.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Augmentation of Endothelial S1PR1 Attenuates Postviral Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2023Review
- Vascular Contribution to Lung Repair and Fibrosis.American journal of respiratory cell and molecular biology · 2023Review
- The Role of Sphingolipids in Regulating Vascular Permeability in Idiopathic Pulmonary Fibrosis.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Fibrotic lung disease, most notably idiopathic pulmonary fibrosis (IPF), is thought to result from aberrant wound-healing responses to repetitive lung injury. Increased vascular permeability is a cardinal response to tissue injury, but whether it is mechanistically linked to lung fibrosis is unknown. We previously described a model in which exaggeration of vascular leak after lung injury shifts the outcome of wound-healing responses from normal repair to pathological fibrosis. Here we report that the fibrosis produced in this model is highly dependent on thrombin activity and its downstream signaling pathways. Direct thrombin inhibition with dabigatran significantly inhibited protease-activated receptor-1 (PAR1) activation, integrin αvβ6 induction, TGF-β activation, and the development of pulmonary fibrosis in this vascular leak-dependent model. We used a potentially novel imaging method - ultashort echo time (UTE) lung magnetic resonance imaging (MRI) with the gadolinium-based, fibrin-specific probe EP-2104R - to directly visualize fibrin accumulation in injured mouse lungs, and to correlate the antifibrotic effects of dabigatran with attenuation of fibrin deposition. We found that inhibition of the profibrotic effects of thrombin can be uncoupled from inhibition of hemostasis, as therapeutic anticoagulation with warfarin failed to downregulate the PAR1/αvβ6/TGF-β axis or significantly protect against fibrosis. These findings have direct and important clinical implications, given recent findings that warfarin treatment is not beneficial in IPF, and the clinical availability of direct thrombin inhibitors that our data suggest could benefit these patients.
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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.