ArticleThe Journal of biological chemistry2008
Transforming growth factor-beta requires its target plasminogen activator inhibitor-1 for cytostatic activity.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 52 citations in OpenAlex.
- Cardiac, oxidative stress, and fibrosis-related biomarkers and new-onset heart failure: Systematic review and meta-analysis.International journal of cardiology. Cardiovascular risk and prevention · 2026Article
- Plasminogen activator inhibitor-1 promotes the proliferation and blocks TGF-β1-dependent growth inhibition of cholesteatoma keratinocytes by ERK signaling.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Targeted Interference with USF2 Binding to the SERPINE1 Proximal Promoter E-Box in Dual Mutant p53Biomedicines · 2026Review
- The Molecular Interplay Between p53-Mediated Ferroptosis and Non-Coding RNAs in Cancer.International journal of molecular sciences · 2025Review
- Role of plasminogen activator inhibitor-1 (PAI-1) in age-related cardiovascular pathophysiology.The journal of cardiovascular aging · 2025Article
- Serpin E1 mediates the induction of renal tubular degeneration and premature senescence upon diabetic insult.Scientific reports · 2023Article
- PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea?International journal of molecular sciences · 2022Review
- Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells.Toxics · 2021Article
- The Genomic Response to TGF-β1 Dictates Failed Repair and Progression of Fibrotic Disease in the Obstructed Kidney.Frontiers in cell and developmental biology · 2021Review
- Targets for protection and mitigation of radiation injury.Cellular and molecular life sciences : CMLS · 2020Review
- Impaired ECM Remodeling and Macrophage Activity Define Necrosis and Regeneration Following Damage in Aged Skeletal Muscle.International journal of molecular sciences · 2020Article
- TGF-β1-p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Review
- TGF-β1/p53 signaling in renal fibrogenesis.Cellular signalling · 2018Review
- Plasminogen Activator Inhibitor-1 Is a Marker and a Mediator of Senescence.Arteriosclerosis, thrombosis, and vascular biology · 2017Review
- A small molecule inhibitor of PAI-1 protects against doxorubicin-induced cellular senescence.Oncotarget · 2016Article
- TGF-β induces p53/Smads complex formation in the PAI-1 promoter to activate transcription.Scientific reports · 2016Article
- TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation.Cell death and differentiation · 2015Article
- Loss of tumour suppressor PTEN expression in renal injury initiates SMAD3- and p53-dependent fibrotic responses.The Journal of pathology · 2015Article
- Tumor suppressor ataxia telangiectasia mutated functions downstream of TGF-β1 in orchestrating profibrotic responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- The basic helix-loop-helix/leucine zipper transcription factor USF2 integrates serum-induced PAI-1 expression and keratinocyte growth.Journal of cellular biochemistry · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytokine transforming growth factor beta (TGFbeta) has strong antiproliferative activity in most normal cells but contributes to tumor progression in the later stages of oncogenesis. It is not fully understood which TGFbeta target genes are causally involved in mediating its cytostatic activity. We report here that suppression of the TGFbeta target gene encoding plasminogen activator inhibitor-1 (PAI-1) by RNA interference leads to escape from the cytostatic activity of TGFbeta both in human keratinocytes (HaCaTs) and primary mouse embryo fibroblasts. Consistent with this, PAI-1 knock-out mouse embryo fibroblasts are also resistant to TGFbeta growth arrest. Conversely, we show that ectopic expression of PAI-1 in proliferating HaCaT cells induces a growth arrest. PAI-1 knockdown does not interfere with canonical TGFbeta signaling as judged by SMAD phosphorylation and induction of bona fide TGFbeta target genes. Instead, knockdown of PAI-1 results in sustained activation of protein kinase B. Significantly, we find that constitutive protein kinase B activity leads to evasion of the growth-inhibitory action of TGFbeta. Our data are consistent with a model in which induction of PAI-1 by TGFbeta is critical for the induction of proliferation arrest.
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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.