ArticleThe Journal of experimental medicine2021
Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Engrailed-1 potentiates mitochondrial transplant neuroprotection in spinal cord ischemia-reperfusion injury.Communications biology · 2026Article
- Exploring the Complexities of TGF-β Signaling in Keloids: Beyond the Classical Smad Pathway.International journal of molecular sciences · 2026Review
- Linezolid-mediated Prevention of Fibroblast Activation and Tissue Fibrosis via Mitochondrial Translation Inhibition.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Fibroblast Lineage Switching as the Developmental Origin of Scarring and Target for Regenerative Healing.Biology · 2026Review
- Dermal Fibroblast Senescence: The Central Hub of Skin Aging-From Intrinsic Dysfunction to Microenvironmental Remodeling.International journal of molecular sciences · 2026Review
- The Molecular Mechanisms and Therapeutic Potentials of Engrailed-1 in Fibrotic Scar Formation Post Glaucoma Filtration Surgery.Investigative ophthalmology & visual science · 2026Article
- Targeted silencing of Engrailed-1 reprograms profibrotic fibroblast lineage for scarless wound healing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Antifibrotic effects of specific targeting of the 5-hydroxytryptamine 2B receptor (5-HTArthritis & rheumatology (Hoboken, N.J.) · 2025Article
- TGF-β drives myofibroblast activation and inflammatory mediator production in vulvar lichen sclerosus.AJOG global reports · 2025Article
- [Pharmacological inhibition of fibrosis exemplified by systemic sclerosis : Possibilities and limits].Innere Medizin (Heidelberg, Germany) · 2025Article
- Integrating spatial and single-cell transcriptomics to characterize mouse long bone fracture healing process.Communications biology · 2025Article
- Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and FibroblastsJournal of functional biomaterials · 2025Article
- Engrailed-1 inactivation leads to scarless skin wound healing through extracellular matrix remodeling.Genes & diseases · 2025Article
- Conserved roles of engrailed: patterning tissues and specifying cell types.Development (Cambridge, England) · 2024Review
- Inactivity-mediated molecular adaptations: Insights from a preclinical model of physical activity reduction.Physiological reports · 2024Article
- Ancestral TALE homeobox protein transcription factor regulates actin dynamics and cellular activities of protozoan parasite Entamoeba invadens.Molecular microbiology · 2024Article
- The role of the cytoskeleton in fibrotic diseases.Frontiers in cell and developmental biology · 2024Review
- CD201Nature · 2023Article
- Single-cell and bulk tissue sequencing unravels the heterogeneity of synovial microenvironment in arthrofibrosis.iScience · 2023Article
- Diversity of Fibroblasts and Their Roles in Wound Healing.Cold Spring Harbor perspectives in biology · 2023Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) is reexpressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and in turn, EN1 mediates the profibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a profibrotic gene expression profile functionally related to cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the reorganization of cytoskeleton during myofibroblast differentiation, in both standard fibroblast culture systems and in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin 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.