ArticleScientific reports2017
The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Collaborative functionality between three types of inflammation in idiopathic pulmonary fibrosis.Nature immunology · 2026Review
- Plasma apolipoprotein E protein attenuates pulmonary fibrosis through LRP1 and PLAU dual receptor-mediated TGF-β/Smad inhibition.Journal of advanced research · 2026Article
- Advances in engineered T cell immunotherapy for autoimmune and other non-oncological diseases.Biomarker research · 2025Review
- 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
- Transcriptomics ofMicroorganisms · 2024Article
- Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis.Respiratory research · 2023Article
- The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Urokinase System in Pathogenesis of Pulmonary Fibrosis: A Hidden Threat of COVID-19.International journal of molecular sciences · 2023Article
- Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer's Disease: A Pilot Study.Journal of Alzheimer's disease reports · 2023Article
- The Association ofInternational journal of molecular sciences · 2022Article
- Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis.ERJ open research · 2022Article
- Contracting scars from fibrin drops.Integrative biology : quantitative biosciences from nano to macro · 2022Article
- The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation.Nature communications · 2021Article
- Transcriptomic Analysis of Polyhexamethyleneguanidine-Induced Lung Injury in Mice after a Long-Term Recovery.Toxics · 2021Article
- Urokinase-type plasminogen activator promotes N-cadherin-mediated synaptic recovery in the ischemic brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Article
- Identification and preclinical development of an anti-proteolytic uPA antibody for rheumatoid arthritis.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Urokinase Plasminogen Activator Overexpression Reverses Established Lung Fibrosis.Thrombosis and haemostasis · 2019Article
- Relationships of protein biomarkers of the urokinase plasminogen activator system with expression of their cognate genes in primary breast carcinomas.Journal of clinical laboratory analysis · 2019Article
- The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis.Aging and disease · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5-15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5-6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung 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.