ArticleOncogene2009
A non-Smad mechanism of fibroblast activation by transforming growth factor-beta via c-Abl and Egr-1: selective modulation by imatinib mesylate.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 83 citations in OpenAlex.
- Trial
- Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy.Frontiers in cardiovascular medicine · 2023Review
- Specific targeting of PDGFRβ in the stroma inhibits growth and angiogenesis in tumors with high PDGF-BB expression.Theranostics · 2020Article
- Emerging targets of disease-modifying therapy for systemic sclerosis.Nature reviews. Rheumatology · 2019Review
- Inhibition of integrin αCell communication and signaling : CCS · 2018Article
- Article
- Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition.Gut and liver · 2017Article
- The progress of early growth response factor 1 and leukemia.Intractable & rare diseases research · 2016Review
- Cytokines in the immunopathology of systemic sclerosis.Seminars in immunopathology · 2015Review
- Transforming growth factor β--at the centre of systemic sclerosis.Nature reviews. Rheumatology · 2014Review
- Prognostic importance of single-nucleotide polymorphisms in IL-6, IL-10, TGF-β1, IFN-γ, and TNF-α genes in chronic phase chronic myeloid leukemia.Genetic testing and molecular biomarkers · 2014Article
- Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni in vitro exhibiting pleiotropic effects.PLoS neglected tropical diseases · 2014Article
- Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1.Arthritis research & therapy · 2014Article
- Leishmania donovani prevents oxidative burst-mediated apoptosis of host macrophages through selective induction of suppressors of cytokine signaling (SOCS) proteins.The Journal of biological chemistry · 2014Article
- Inhibition of radiation-induced skin fibrosis with imatinib.International journal of radiation biology · 2013Article
- Pharmacology and rationale for imatinib in the treatment of scleroderma.Journal of experimental pharmacology · 2013Review
- Egr-1: new conductor for the tissue repair orchestra directs harmony (regeneration) or cacophony (fibrosis).The Journal of pathology · 2013Review
- The Role of TGF-β Receptors in Fibrosis.The open rheumatology journal · 2012Article
- Fibrosis in systemic sclerosis: common and unique pathobiology.Fibrogenesis & tissue repair · 2012Article
- Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities.Nature reviews. Rheumatology · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The nonreceptor protein tyrosine kinase c-Abl regulates cell proliferation and survival. Recent studies provide evidence that implicate c-Abl as a mediator for fibrotic responses induced by transforming growth factor-beta (TGF-beta), but the precise mechanisms underlying this novel oncogene function are unknown. Here, we report that when expressed in normal fibroblasts, a constitutively active mutant of Abl that causes chronic myelogenous leukemia (CML) stimulated the expression and transcriptional activity of the early growth response factor 1 (Egr-1). Mouse embryonic fibroblasts (MEFs), lacking c-Abl, were resistant to TGF-beta stimulation. Responsiveness of these MEFs to TGF-beta could be rescued by wild-type c-Abl, but not by a kinase-deficient mutant form of c-Abl. Furthermore, Abl kinase activity was necessary for the induction of Egr-1 by TGF-beta in normal fibroblasts, and Egr-1 was required for stimulation of collagen by Bcr-Abl. Lesional skin fibroblasts in mice with bleomycin-induced fibrosis of skin displayed evidence of c-Abl activation in situ, and elevated phospho-c-Abl correlated with increased local expression of Egr-1. Collectively, these results position Egr-1 downstream of c-Abl in the fibrotic response, delineate a novel Egr-1-dependent intracellular signaling mechanism that underlies the involvement of c-Abl in certain TGF-beta responses, and identify Egr-1 as a target of inhibition by imatinib. Furthermore, the findings show in situ activation of c-Abl paralleling the upregulated tissue expression of Egr-1 that accompanies fibrosis. Pharmacological targeting of c-Abl and its downstream effector pathways may, therefore, represent a novel therapeutic approach to blocking TGF-beta-dependent fibrotic processes.
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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.