ArticleMolecular biology of the cell2009
Transforming growth factor beta1-mediated activation of the smooth muscle alpha-actin gene in human pulmonary myofibroblasts is inhibited by tumor necrosis factor-alpha via mitogen-activated protein kinase kinase 1-dependent induction of the Egr-1 transcriptional repressor.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Receptor tyrosine kinase ligands and inflammatory cytokines cooperatively suppress the fibrogenic activity in temporomandibular-joint-derived fibroblast-like synoviocytes via mitogen-activated protein kinase kinase/extracellular signal-regulated kinase.Experimental and therapeutic medicine · 2020Article
- Quantification of uncertainty in a new network model of pulmonary arterial adventitial fibroblast pro-fibrotic signalling.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Article
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- Acceleration Mechanisms of Skin Wound Healing by Autologous Micrograft in Mice.International journal of molecular sciences · 2017Article
- β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.Investigative ophthalmology & visual science · 2017Article
- Hypoxia-inducible factor-1α promotes glomerulosclerosis and regulates COL1A2 expression through interactions with Smad3.Kidney international · 2016Article
- Epidermal growth factor inhibits transforming growth factor-β-induced fibrogenic differentiation marker expression through ERK activation.Cellular signalling · 2014Article
- Genetic factors regulating lung vasculature and immune cell functions associate with resistance to pneumococcal infection.PloS one · 2014Article
- Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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- Myofibroblast differentiation and survival in fibrotic disease.Expert reviews in molecular medicine · 2011Review
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- NADPH oxidase 4 mediates TGF-β-induced smooth muscle α-actin via p38MAPK and serum response factor.Free radical biology & medicine · 2011Article
- Angiotensin II-regulated transcription regulatory genes in adrenal steroidogenesis.Physiological genomics · 2010Article
- The effect of the pro-inflammatory cytokine tumor necrosis factor-alpha on human joint capsule myofibroblasts.Arthritis research & therapy · 2010Article
- PDGF-Ralpha gene expression predicts proliferation, but PDGF-A suppresses transdifferentiation of neonatal mouse lung myofibroblasts.Respiratory research · 2009Article
- Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Transforming growth factor (TGF) beta1 is a mediator of myofibroblast differentiation in healing wounds in which it activates transcription of the smooth muscle alpha-actin (SMalphaA) gene via dynamic interplay of nuclear activators and repressors. Targeting components of TGFbeta1 signaling may be an effective strategy for controlling myofibroblasts in chronic fibrotic diseases. We examined the ability of proinflammatory tumor necrosis factor (TNF)-alpha to antagonize TGFbeta1-mediated human pulmonary myofibroblast differentiation. TNF-alpha abrogated TGFbeta1-induced SMalphaA gene expression at the level of transcription without disrupting phosphorylation of regulatory Smads. Intact mitogen-activated protein kinase kinase (Mek)-extracellular signal-regulated kinase (Erk) kinase signaling was required for myofibroblast repression by TNF-alpha via induction of the early growth response factor-1 (Egr-1) DNA-binding protein. Egr-1 bound to the GC-rich SPUR activation element in the SMalphaA promoter and potently suppressed Smad3- and TGFbeta1-mediated transcription. Reduction in Smad binding to the SMalphaA promoter in TNF-alpha-treated myofibroblasts was accompanied by an increase in Egr-1 and YB-1 repressor binding, suggesting that the molecular mechanism underlying repression may involve competitive interplay between Egr-1, YB-1, and Smads. The ability of TNF-alpha to attenuate myofibroblast differentiation via modulation of a Mek1/Erk/Egr-1 regulatory axis may be useful in designing new therapeutic targets to offset destructive tissue remodeling in chronic fibrotic disease.
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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.