ArticleScience translational medicine2019
PAI-1 augments mucosal damage in colitis.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Epidemiology and Risk Factors of Portal Venous System Thrombosis in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2021Pooled it
- The Serine Protease-Serine Protease Inhibitor Regulatory Network in Inflammatory Bowel Disease: From Molecular Mechanisms to Novel Therapeutic Horizons.Journal of advanced research · 2026Review
- A microbiome meta-transcriptomics pipeline identifies a neutrophil elastase inhibitor that protects the colonic epithelial barrier.Signal transduction and targeted therapy · 2026Article
- Pre-Treatment with Estradiol, But not Progesterone, Exacerbates DSS Colitis: Dysregulated Innate Immunity and Impaired Epithelial Damage Response.Inflammation · 2026Article
- SERPINE1 drives ferroptosis in acute respiratory distress syndrome by disrupting mitochondrial NADRedox biology · 2026Article
- Tissue transcriptional programs stratify Crohn's disease by therapeutic response and clinical outcomes.Scientific reports · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Virus-derived serpin reduces immuno-coagulopathic damage in murine colitis by targeting the urokinase-type plasminogen activator receptor (uPAR) and complement.Scientific reports · 2025Article
- Targeting Plasminogen Activator Inhibitor-1 with a Novel Small Molecule Inhibitor Attenuates Lung Fibrosis.Research square · 2025Article
- MCT4 inhibition attenuates inflammatory response toFrontiers in immunology · 2025Article
- Ileal Paneth Cell Phenotype is a Cellular Biomarker for Pouch Complications in Ulcerative Colitis.Journal of Crohn's & colitis · 2024Article
- Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms.Inflammatory bowel diseases · 2024Review
- Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.Journal of Crohn's & colitis · 2024Article
- Article
- A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis.Biomedicines · 2023Review
- Using LLMs and Explainable ML to Analyze Biomarkers at Single-Cell Level for Improved Understanding of Diseases.Biomolecules · 2023Article
- The IL-17 family in diseases: from bench to bedside.Signal transduction and targeted therapy · 2023Review
- MRTF-A gain-of-function in mice impairs homeostatic renewal of the intestinal epithelium.Cell death & disease · 2023Article
- Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.Science (New York, N.Y.) · 2023Article
- Multi-Faceted Role of Cancer-Associated Adipocytes in Colorectal Cancer.Biomedicines · 2023Review
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
There is a major unmet clinical need to identify pathways in inflammatory bowel disease (IBD) to classify patient disease activity, stratify patients that will benefit from targeted therapies such as anti-tumor necrosis factor (TNF), and identify new therapeutic targets. In this study, we conducted global transcriptome analysis to identify IBD-related pathways using colon biopsies, which highlighted the coagulation gene pathway as one of the most enriched gene sets in patients with IBD. Using this gene-network analysis across 14 independent cohorts and 1800 intestinal biopsies, we found that, among the coagulation pathway genes, plasminogen activator inhibitor-1 (PAI-1) expression was highly enriched in active disease and in patients with IBD who did not respond to anti-TNF biologic therapy and that PAI-1 is a key link between the epithelium and inflammation. Functionally, PAI-1 and its direct target, the fibrinolytic protease tissue plasminogen activator (tPA), played an important role in regulating intestinal inflammation. Intestinal epithelial cells produced tPA, which was protective against chemical and mechanical-mediated colonic injury in mice. In contrast, PAI-1 exacerbated mucosal damage by blocking tPA-mediated cleavage and activation of anti-inflammatory TGF-β, whereas the inhibition of PAI-1 reduced both mucosal damage and inflammation. This study identifies an immune-coagulation gene axis in IBD where elevated PAI-1 may contribute to more aggressive disease.
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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.