ArticleJCI insight2021
Myofibroblast dedifferentiation proceeds via distinct transcriptomic and phenotypic transitions.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- Macrophage Mistargeting During Direct Cardiac Reprogramming: Cardiac-Associated Responses, Polarization, and Cell Death.Biomedicines · 2026Article
- MRC2-mediated collagen internalization is reduced in fibrotic lung fibroblasts and increased upon phenotypic dedifferentiation.JCI insight · 2026Article
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- Modulatory effects of Pioglitazone on the CAF-driven malignant phenotype in cervical cancer: an in vitro bidirectional study.Discover oncology · 2026Article
- Longitudinal Single-Cell RNA-seq Profiling of Lung Cell Phenotypes, Signaling, and Cross-talk During Fibrosis Resolution.bioRxiv : the preprint server for biology · 2026Article
- Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Prostaglandin EbioRxiv : the preprint server for biology · 2026Article
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Simultaneous inhibition of ID1 and ID3 mitigates fibroblast activation via cell cycle and MEK/ERK pathways in pulmonary fibrosis.Theranostics · 2026Article
- Mechanistic basis for the antifibrotic actions of cAMP-based therapies.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- B. adolescentis alleviates inflammation and suppresses PGE2 through remodling gut microbiota to attenuate pulmonary fibrosis in aging mice.NPJ science of food · 2025Article
- Epigenetic Reprogramming Via Sodium Butyrate Induces Corneal Myofibroblast Dedifferentiation In Vitro and Inhibits Fibrosis In Vivo.Investigative ophthalmology & visual science · 2025Article
- Scar wars: the viral menace.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Insights into the Cellular and Molecular Mechanisms behind the Antifibrotic Effects of Nerandomilast.American journal of respiratory cell and molecular biology · 2025Article
- Reimagining Fibrosis Research, Outcomes, and Therapeutics Through the Lens of Resolution.Seminars in respiratory and critical care medicine · 2025Review
- Distinct cAMP Regulation in Scleroderma Lung and Skin Myofibroblasts Governs Their Dedifferentiation via p38α Inhibition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Targeting the Epigenetic Regulator CBX5 Promotes Fibroblast Metabolic Reprogramming and Inhibits Lung Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Succinate aggravates pulmonary fibrosis through the succinate/SUCNR1 axis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Myofibroblasts are the major cellular source of collagen, and their accumulation - via differentiation from fibroblasts and resistance to apoptosis - is a hallmark of tissue fibrosis. Clearance of myofibroblasts by dedifferentiation and restoration of apoptosis sensitivity has the potential to reverse fibrosis. Prostaglandin E2 (PGE2) and mitogens such as FGF2 have each been shown to dedifferentiate myofibroblasts, but - to our knowledge - the resultant cellular phenotypes have neither been comprehensively characterized or compared. Here, we show that PGE2 elicited dedifferentiation of human lung myofibroblasts via cAMP/PKA, while FGF2 utilized MEK/ERK. The 2 mediators yielded transitional cells with distinct transcriptomes, with FGF2 promoting but PGE2 inhibiting proliferation and survival. The gene expression pattern in fibroblasts isolated from the lungs of mice undergoing resolution of experimental fibrosis resembled that of myofibroblasts treated with PGE2 in vitro. We conclude that myofibroblast dedifferentiation can proceed via distinct programs exemplified by treatment with PGE2 and FGF2, with dedifferentiation occurring in vivo most closely resembling the former.
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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.