ArticleGene2014
A far-upstream AP-1/Smad binding box regulates human NOX4 promoter activation by transforming growth factor-β.
Article in Gene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Experimental workflows for the accurate identification of mitochondrial redox events.Redox biology · 2026Review
- Tanshinone IIA Attenuates Pulmonary Fibrosis via Dual Inhibition of JNK and Smad Signaling.Antioxidants (Basel, Switzerland) · 2026Article
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Review
- ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.Cancer research · 2022Article
- Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target.Journal of clinical medicine · 2021Review
- The hydrogen-peroxide producing NADPH oxidase 4 does not limit neointima development after vascular injury in mice.Redox biology · 2021Article
- A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis.Open heart · 2021Article
- TGF-β2 Promotes Oxidative Stress in Human Trabecular Meshwork Cells by Selectively Enhancing NADPH Oxidase 4 Expression.Investigative ophthalmology & visual science · 2021Article
- ENERGY SENSING PATHWAYS IN AGING AND CHRONIC LUNG DISEASE.Transactions of the American Clinical and Climatological Association · 2020Article
- The Chromatin Remodeler Brg1 Integrates ROS Production and Endothelial-Mesenchymal Transition to Promote Liver Fibrosis in Mice.Frontiers in cell and developmental biology · 2019Article
- Inhibition of Nox4-dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal-mediated protumorigenic interactions.International journal of cancer · 2018Article
- c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer.Oncology reports · 2017Article
- Fibroblast-specific TGF-β-Smad2/3 signaling underlies cardiac fibrosis.The Journal of clinical investigation · 2017Article
- Paradoxical roles of dual oxidases in cancer biology.Free radical biology & medicine · 2017Review
- Histone modifications affect differential regulation of TGFβ- induced NADPH oxidase 4 (NOX4) by wild-type and mutant p53.Oncotarget · 2017Article
- The Role of NOX4 and TRX2 in Angiogenesis and Their Potential Cross-Talk.Antioxidants (Basel, Switzerland) · 2017Review
- Brd4 inhibition attenuates unilateral ureteral obstruction-induced fibrosis by blocking TGF-β-mediated Nox4 expression.Redox biology · 2017Article
- Coordinate activities of BRD4 and CDK9 in the transcriptional elongation complex are required for TGFβ-induced Nox4 expression and myofibroblast transdifferentiation.Cell death & disease · 2017Article
- Oxidative Stress in Oral Diseases: Understanding Its Relation with Other Systemic Diseases.Frontiers in physiology · 2017Review
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Authors and funding
5 authors.
Funding
Abstract
NADPH oxidase 4 (NOX4) is a member of the NADPH oxidase gene family that regulates cellular differentiation, innate immunity and tissue fibrosis. Transforming growth factor-β (TGF-β1) is known to induce expression of NOX4 mRNA in mesenchymal cells. However, the mechanisms of transcriptional regulation of NOX4 are not well understood. In this study, we examined the transcriptional regulation of NOX4 in human lung fibroblasts by TGF-β1. Five promoter-reporter constructs containing DNA fragments of 0.74kb, 1.35kb, 1.84kb, 3.97kb and 4.76kb upstream from the transcriptional start site (TSS) of the human NOX4 gene were generated and their relative responsiveness to TGF-β1 analyzed. TGF-β1-induced NOX4 gene promoter activation requires a region between -3.97kb and -4.76kb. Bioinformatics analysis revealed a 15bp AP-1/Smad binding element in this region. Mutation or deletion of either the AP-1 or the Smad element attenuated TGF-β1 responsiveness of the -4.76kb NOX4 promoter. Furthermore, insertion of this AP-1/Smad box conferred TGF-β1 inducibility to the non-responsive -3.97kb NOX4 promoter construct. Chromatin immunoprecipitation analysis indicated that phospho-Smad3 and cJun associate with this element in a TGF-β1-inducible manner. These results demonstrate that the AP-1/Smad box located between 3.97kb and 4.76kb upstream of the TSS site of the NOX4 promoter is essential for NOX4 gene transcription induced by TGF-β1 in human lung fibroblasts. Our study provides insights into the molecular mechanisms of NOX4 gene expression, informing novel therapeutic approaches to interfere with upregulation of NOX4 in diseases characterized by activation of the TGF-β1/NOX4 pathway.
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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.