ArticleThe American journal of pathology2008
Smad-independent transforming growth factor-beta regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 98 citations in OpenAlex.
- Low-dose nicotine enhances arecoline-induced human oral mucosa fibroblast proliferation by stabilizing Egr-1 protein.Odontology · 2026Article
- Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse.Development & reproduction · 2026Review
- Topical medium-length PDRN enhances dermal extracellular matrix repair in photodamaged skin via PI3K-Akt/TGF-β-regulated pathways.PloS one · 2026Article
- Smad4 and Eomes converge on a shared transcriptional program associated with inflammatory CD8 T-cell differentiation.Frontiers in immunology · 2026Article
- Integrated bulk and single-cell transcriptomics identifies shared and specific immune signatures in Takayasu Arteritis.Arthritis research & therapy · 2025Article
- Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of patients with systemic sclerosis.Nature communications · 2025Article
- The Role of Signalling Pathways in Myocardial Fibrosis in Hypertrophic Cardiomyopathy.Reviews in cardiovascular medicine · 2025Review
- The Role of Autophagy and Apoptosis in Affected Skin and Lungs in Patients with Systemic Sclerosis.International journal of molecular sciences · 2023Review
- Melatonin and TGF-β-Mediated Release of Extracellular Vesicles.Metabolites · 2023Review
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- Periostin-An inducer of pro-fibrotic phenotype in monocytes and monocyte-derived macrophages in systemic sclerosis.PloS one · 2023Article
- Defining the spatial-molecular map of fibrotic tendon healing and the drivers of Scleraxis-lineage cell fate and function.Cell reports · 2022Article
- Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy.Drug delivery · 2021Review
- miR-23a-3p regulates the inflammatory response and fibrosis in diabetic kidney disease by targeting early growth response 1.In vitro cellular & developmental biology. Animal · 2021Article
- 17,20S(OH)International journal of molecular sciences · 2021Article
- Genome-Wide Reduction in Chromatin Accessibility and Unique Transcription Factor Footprints in Endothelial Cells and Fibroblasts in Scleroderma Skin.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Early growth response 1 (EGR1) activation in initial stages of host-pathogen interactions.Molecular biology reports · 2021Review
- Elucidating the cellular mechanism for E2-induced dermal fibrosis.Arthritis research & therapy · 2021Article
- Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity.Science translational medicine · 2020Article
- Activin A-Mediated Regulation of XT-I in Human Skin Fibroblasts.Biomolecules · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Transforming growth factor-beta (TGF-beta) plays a key role in scleroderma pathogenesis. The transcription factor early growth response-1 (Egr-1) mediates the stimulation of collagen transcription elicited by TGF-beta and is necessary for the development of pulmonary fibrosis in mice. Here, we report that TGF-beta causes a time- and dose-dependent increase in Egr-1 protein and mRNA levels and enhanced transcription of the Egr-1 gene via serum response elements in normal fibroblasts. The ability of TGF-beta to stimulate Egr-1 was preserved in Smad3-null mice and in explanted Smad3-null fibroblasts. The response was blocked by a specific mitogen-activated protein kinase kinase 1 (MEK1) inhibitor but not by an ALK5 kinase inhibitor. Furthermore, MEK1 was phosphorylated by TGF-beta, which was sufficient to drive Egr-1 transactivation. Stimulation by TGF-beta enhanced the transcriptional activity of Elk-1 via the MEK-extracellular signal-regulated kinase 1/2 pathway. Bleomycin-induced scleroderma in the mouse was accompanied by increased Egr-1 accumulation in lesional fibroblasts. Furthermore, biopsies of lesional skin and lung from patients with scleroderma showed increased Egr-1 levels, which were highest in early diffuse disease. Moreover, both Egr-1 mRNA and protein were elevated in explanted scleroderma skin fibroblasts in vitro. Together, these findings define a Smad-independent TGF-beta signal transduction mechanism that underlies the stimulation of Egr-1, demonstrate for the first time sustained Egr-1 up-regulation in fibrotic lesions and suggests that Egr-1 has a role in the induction and progression of fibrosis.
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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.