ArticleThe American journal of pathology2017
Inhibition of Glycogen Synthase Kinase 3β Blocks Mesomesenchymal Transition and Attenuates Streptococcus pneumonia-Mediated Pleural Injury in Mice.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04218071 (Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta), which is not on this map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, as a Single Agent or Combined With Ruxolitinib, in Patients With Myelofibrosis
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells-Peritoneal Stroma Interactions.Frontiers in immunology · 2021Pooled it
- Extracellular Vesicles Contribute to the Pathophysiology and Progression of Pleural Fibrosis by Promoting Mesothelial-to-Mesenchymal Transition and Neoangiogenesis.American journal of respiratory cell and molecular biology · 2025Article
- The Role of Tuftelin-1 in Mesomesenchymal Transition of Pleural Mesothelial Cells and the Progression of Pleural Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Perspective and update: intrapleural fibrinolytic therapy for pleural infections and other forms of pleural organization.Respiratory research · 2025Review
- GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model.International journal of molecular sciences · 2024Review
- The mTORC2/SGK1/NDRG1 Signaling Axis Is Critical for the Mesomesenchymal Transition of Pleural Mesothelial Cells and the Progression of Pleural Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- Myo5b Transports Fibronectin-Containing Vesicles and Facilitates FN1 Secretion from Human Pleural Mesothelial Cells.International journal of molecular sciences · 2022Article
- Early IL-17A production helps establish Mycobacterium intracellulare infection in mice.PLoS pathogens · 2022Article
- Caveolin-1-Derived Peptide Reduces ER Stress and Enhances Gelatinolytic Activity in IPF Fibroblasts.International journal of molecular sciences · 2022Article
- DOCK-t(w)o Pleural Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- DOCK2 Promotes Pleural Fibrosis by Modulating Mesothelial to Mesenchymal Transition.American journal of respiratory cell and molecular biology · 2022Article
- Update on Novel Targeted Therapy for Pleural Organization and Fibrosis.International journal of molecular sciences · 2022Review
- Insights from DOCK2 in cell function and pathophysiology.Frontiers in molecular biosciences · 2022Review
- Intratracheally Inhalable Nifedipine-Loaded Chitosan-PLGA Nanocomposites as a Promising Nanoplatform for Lung Targeting: Snowballed ProtectionPharmaceuticals (Basel, Switzerland) · 2021Article
- TGF-β regulation of the uPA/uPAR axis modulates mesothelial-mesenchymal transition (MesoMT).Scientific reports · 2021Article
- Urokinase-type plasminogen activator-mediated crosstalk between N-cadherin and β-catenin promotes wound healing.Journal of cell science · 2021Article
- NOX1 Promotes Mesothelial-Mesenchymal Transition through Modulation of Reactive Oxygen Species-mediated Signaling.American journal of respiratory cell and molecular biology · 2021Article
- 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
- From Bedside to the Bench-A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema.Frontiers in pharmacology · 2021Review
- Glycogen synthase kinase-3β: a promising candidate in the fight against fibrosis.Theranostics · 2020Review
Corrections and comments
- Erratum issuedCorrection.2018
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Pleural loculation affects about 30,000 patients annually in the United States and in severe cases can resolve with restrictive lung disease and pleural fibrosis. Pleural mesothelial cells contribute to pleural rind formation by undergoing mesothelial mesenchymal transition (MesoMT), whereby they acquire a profibrotic phenotype characterized by increased expression of α-smooth muscle actin and collagen 1. Components of the fibrinolytic pathway (urokinase plasminogen activator and plasmin) are elaborated in pleural injury and strongly induce MesoMT in vitro. These same stimuli enhance glycogen synthase kinase (GSK)-3β activity through increased phosphorylation of Tyr-216 in pleural mesothelial cells and GSK-3β mobilization from the cytoplasm to the nucleus. GSK-3β down-regulation blocked induction of MesoMT. Likewise, GSK-3β inhibitor 9ING41 blocked induction of MesoMT and reversed established MesoMT. Similar results were demonstrated in a mouse model of Streptococcus pneumoniae-induced empyema. Intraperitoneal administration of 9ING41, after the induction of pleural injury, attenuated injury progression and improved lung function (lung volume and compliance; P < 0.05 compared with untreated and vehicle controls). MesoMT marker α-smooth muscle actin was reduced in 9ING41-treated mice. Pleural thickening was also notably reduced in 9ING41-treated mice (P < 0.05). Collectively, these studies identify GSK-3β as a newly identified target for amelioration of empyema-related pleural fibrosis and provide a strong rationale for further investigation of GSK-3β signaling in the control of MesoMT and pleural injury.
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What OpenQuestion holds
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.