ArticleAmerican journal of respiratory cell and molecular biology2007
Gut-enriched Krüppel-like factor interaction with Smad3 inhibits myofibroblast differentiation.
Article in American journal of respiratory cell and molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 64 citations in OpenAlex.
- TGF-β: The Molecular Mechanisms of Atherosclerosis - insights into SMAD Pathways and Gene Therapy Prospects.Current medicinal chemistry · 2026Review
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- Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma.Communications biology · 2023Article
- Lysyl oxidase like-2 in fibrosis and cardiovascular disease.American journal of physiology. Cell physiology · 2023Review
- Inhibition of miR-25 Ameliorates Cardiac Dysfunction and Fibrosis by Restoring Krüppel-like Factor 4 Expression.International journal of molecular sciences · 2023Article
- Phosphorus May Induce Phenotypic Transdifferentiation of Vascular Smooth Muscle Cells through the Reduction of microRNA-145.Nutrients · 2023Article
- KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.JCI insight · 2022Article
- Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis.Nature communications · 2021Article
- Noncanonical Wnt Signaling Promotes Myofibroblast Differentiation in Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2021Article
- Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite.Frontiers in pharmacology · 2021Review
- Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation.Circulation research · 2020Review
- Glucosamine impedes transforming growth factor β1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.Journal of biomedical science · 2019Article
- Mechanisms of Ventilator-induced Lung Injury: Is the Elafin in the Room?American journal of respiratory cell and molecular biology · 2018Article
- Fibroblast-specific TGF-β-Smad2/3 signaling underlies cardiac fibrosis.The Journal of clinical investigation · 2017Article
- BMP signaling orchestrates a transcriptional network to control the fate of mesenchymal stem cells in mice.Development (Cambridge, England) · 2017Article
- Article
- Dibutyryl-cAMP attenuates pulmonary fibrosis by blocking myofibroblast differentiation via PKA/CREB/CBP signaling in rats with silicosis.Respiratory research · 2017Article
- Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment.Nature communications · 2016Article
- Notch in fibrosis and as a target of anti-fibrotic therapy.Pharmacological research · 2016Review
- Endothelial Plasticity: Shifting Phenotypes through Force Feedback.Stem cells international · 2016Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Gut-enriched Krüppel-like factor (GKLF) has been reported to partially inhibit alpha-smooth muscle actin (alpha-SMA) gene transcription by competing for binding to the TGF-beta control element (TCE) with known activators such as Sp1 and other Krüppel-like factors. This incomplete inhibition via the TCE suggests an additional mechanism, which was evaluated in this study. The results showed that an alpha-SMA promoter mutated in the TCE remained susceptible to inhibition by GKLF in rat lung fibroblasts consistent with the existence of an additional TCE-independent mechanism. Since TGF-beta- induced alpha-SMA expression is Smad3-dependent, potential interaction between GKLF and Smad3 was examined as a basis for this additional inhibitory mechanism. Co-immunoprecipitation and yeast two-hybrid assays revealed that GKLF could bind Smad3 through the Smad3 MH2 domain. Electrophoretic mobility shift assays and ChIP assay indicated that this GKLF-Smad3 interaction inhibited Smad3 binding to the Smad3-binding element (SBE) in the alpha-SMA promoter, and the activity of an SBE containing artificial promoter. Further analysis using smad3(-/-) fibroblasts confirmed that the TCE-independent inhibition by GKLF was dependent on Smad3. These data taken together suggest that in addition to inhibition via the TCE, GKLF represses alpha-SMA gene expression by interacting with Smad3 to prevent Smad3 binding to the SBE. It represents the first evidence to directly link GKLF with Smad3, a key intracellular mediator of TGF-beta signaling, which should lead to a clearer understanding of the mechanism of how GKLF regulates TGF-beta-induced gene expression.
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