ArticlePloS one2016
Inhibition of Plasminogen Activator Inhibitor-1 Attenuates Transforming Growth Factor-β-Dependent Epithelial Mesenchymal Transition and Differentiation of Fibroblasts to Myofibroblasts.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model.JCI insight · 2026Article
- Abnormalities of liver sinusoidal endothelial cells in primary biliary cholangitis.World journal of experimental medicine · 2026Article
- Plasminogen Activator Inhibitor-1 Mediates Tolerance to Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer.Molecular cancer therapeutics · 2026Article
- Targeting Plasminogen Activator Inhibitor-1 with a Novel Small Molecule Inhibitor Attenuates Lung Fibrosis.Research square · 2025Article
- Hematologic and Immunologic Overlap Between COVID-19 and Idiopathic Pulmonary Fibrosis.Journal of clinical medicine · 2025Review
- Liver steatosis is positively associated with plasminogen activator inhibitor-1 in apparently healthy individuals with overweight and obesity: A FibroScan-Based Cross-Sectional study.Journal of translational medicine · 2025Article
- Serum profiling of uPA, PAI-1, and suPAR in systemic sclerosis: a preliminary study on analytical aspects and associations with microvascular and fibrotic manifestations.Frontiers in immunology · 2025Article
- What Is on the Horizon for Treatments in Idiopathic Pulmonary Fibrosis?Journal of clinical medicine · 2024Review
- Review
- PAI-1 mediates TGF-β1-induced myofibroblast activation in tenocytes via mTOR signaling.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Emergent Peptides of the Antifibrotic Arsenal: Taking Aim at Myofibroblast Promoting Pathways.Biomolecules · 2023Review
- Targeting fibrotic signaling pathways by EGCG as a therapeutic strategy for uterine fibroids.Scientific reports · 2023Article
- Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats.Journal of the Association for Research in Otolaryngology : JARO · 2023Article
- Article
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- miR-486 improves fibrotic activity in myocardial infarction by targeting SRSF3/p21-Mediated cardiac myofibroblast senescence.Journal of cellular and molecular medicine · 2022Article
- Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial-mesenchymal transition.Life science alliance · 2022Article
- Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.NPJ Regenerative medicine · 2022Article
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) is central during the pathogenesis of pulmonary fibrosis, in which the plasminogen activator inhibitor-1 (PAI-1) also has an established role. TGF-β is also known to be the strongest inducer of PAI-1. To investigate the link between PAI-1 and TGF-β in fibrotic processes, we evaluated the effect of SK-216, a PAI-1-specific inhibitor, in TGF-β-dependent epithelial-mesenchymal transition (EMT) and fibroblast to myofibroblast differentiation. In human alveolar epithelial A549 cells, treatment with TGF-β induced EMT, whereas co-treatment with SK-216 attenuated the occurrence of EMT. The inhibition of TGF-β-induced EMT by SK-216 was also confirmed in the experiment using murine epithelial LA-4 cells. Blocking EMT by SK-216 inhibited TGF-β-induced endogenous production of PAI-1 and TGF-β in A549 cells as well. These effects of SK-216 were not likely mediated by suppressing either Smad or ERK pathways. Using human lung fibroblast MRC-5 cells, we demonstrated that SK-216 inhibited TGF-β-dependent differentiation of fibroblasts to myofibroblasts. We also observed this inhibition by SK-216 in human primary lung fibroblasts. Following these in vitro results, we tested oral administration of SK-216 into mice injected intratracheally with bleomycin. We found that SK-216 reduced the degree of bleomycin-induced pulmonary fibrosis in mice. Although the precise mechanisms underlying the link between TGF-β and PAI-1 regarding fibrotic process were not determined, PAI-1 seems to act as a potent downstream effector on the pro-fibrotic property of TGF-β. In addition, inhibition of PAI-1 activity by a PAI-1 inhibitor exerts an antifibrotic effect even in vivo. These data suggest that targeting PAI-1 as a downstream effector of TGF-β could be a promising therapeutic strategy for pulmonary fibrosis.
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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.