ArticleThe Journal of biological chemistry2014
Prostaglandin E2 inhibits α-smooth muscle actin transcription during myofibroblast differentiation via distinct mechanisms of modulation of serum response factor and myocardin-related transcription factor-A.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 84 citations in OpenAlex.
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Roflumilast Inhibits Fibrogenic Activation in Human Intestinal Myofibroblasts via Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling.International journal of molecular sciences · 2026Article
- Epithelial Integrins Coordinate Cellular Crosstalk Through the Regulation of Cytokines During Tissue Remodeling.International journal of molecular sciences · 2026Review
- 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
- Insights into the Cellular and Molecular Mechanisms behind the Antifibrotic Effects of Nerandomilast.American journal of respiratory cell and molecular biology · 2025Article
- Magnesium ions attenuate tendon graft fibrosis during its ligamentization after ACL reconstruction through modulation of fibroblast to myofibroblast trans-differentiation by promoting PGE2 secretion.Bioactive materials · 2025Article
- Cryo-mtscATAC-seq for single-cell mitochondrial DNA genotyping and clonal tracing in archived human tissues.bioRxiv : the preprint server for biology · 2025Article
- 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
- Regulation of myofibroblast dedifferentiation in pulmonary fibrosis.Respiratory research · 2024Review
- Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Sini decoction against renal fibrosis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution.The Journal of clinical investigation · 2024Article
- Prostaglandin EFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway.Open medicine (Warsaw, Poland) · 2023Article
- KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.JCI insight · 2022Article
- Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling.Reproductive medicine and biology · 2022Article
- Ogerin mediated inhibition of TGF-β(1) induced myofibroblast differentiation is potentiated by acidic pH.PloS one · 2022Article
- Changing prostaglandin E2 (PGEReproductive medicine and biology · 2022Article
- Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition.American journal of respiratory cell and molecular biology · 2022Article
- Involvement of TLR4 signaling regulated-COX2/PGE2 axis in liver fibrosis induced by Schistosoma japonicum infection.Parasites & vectors · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Differentiation of lung fibroblasts into contractile protein-expressing myofibroblasts by transforming growth factor-β1 (TGF-β1) is a critical event in the pathogenesis of pulmonary fibrosis. Transcription of the contractile protein α-smooth muscle actin (α-SMA) is mediated by the transcription factor serum-response factor (SRF) along with its co-activator, myocardin-related transcription factor-A (MRTF-A). The endogenous lipid mediator prostaglandin E2 (PGE2) exerts anti-fibrotic effects, including the inhibition of myofibroblast differentiation. However, the mechanism by which PGE2 inhibits α-SMA expression is incompletely understood. Here, we show in normal lung fibroblasts that PGE2 reduced the nuclear accumulation of MRTF-A·SRF complexes and consequently inhibited α-SMA promoter activation. It did so both by independently inhibiting SRF gene expression and nuclear import of MRTF-A. We identified that p38 MAPK is critical for TGF-β1-induced SRF gene expression and that PGE2 inhibition of SRF expression is associated with its ability to inhibit p38 activation. Its inhibition of MRTF-A import occurs via activation of cofilin 1 and inactivation of vasodilator-stimulated phosphoprotein. Similar effects of PGE2 on SRF gene expression were observed in fibroblasts from the lungs of patients with idiopathic pulmonary fibrosis. Thus, PGE2 is the first substance described to prevent myofibroblast differentiation by disrupting, via distinct mechanisms, the actions of both SRF and MRTF-A.
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