ArticleThe American journal of pathology2007
Immunomodulator FTY720 induces myofibroblast differentiation via the lysophospholipid receptor S1P3 and Smad3 signaling.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 89 citations in OpenAlex.
- Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial.Journal of neurology, neurosurgery, and psychiatry · 2014Trial
- Mechanistic insights and therapeutic potential of sphingosine‑1‑phosphate in the development of pulmonary fibrosis (Review).Molecular medicine reports · 2026Review
- Sphingolipids: drivers of cardiac fibrosis and atrial fibrillation.Journal of molecular medicine (Berlin, Germany) · 2024Review
- AFrontiers in cardiovascular medicine · 2024Article
- The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- The Role of Sphingolipids in Regulating Vascular Permeability in Idiopathic Pulmonary Fibrosis.Biomedicines · 2023Review
- Potentiation of Sphingolipids and TGF-β in the human corneal stroma reveals intricate signaling pathway crosstalks.Experimental eye research · 2023Article
- Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases.Biomolecules · 2023Review
- Sphk1 and Sphk2 Differentially Regulate Erythropoietin Synthesis in Mouse Renal Interstitial Fibroblast-like Cells.International journal of molecular sciences · 2022Article
- Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage.Frontiers in physiology · 2021Review
- The role of sphingosine 1-phosphate and its receptors in cardiovascular diseases.Journal of cellular and molecular medicine · 2020Review
- Sphingosine-1-phosphate pathway in renal fibrosis.American journal of physiology. Renal physiology · 2018Review
- Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.PloS one · 2018Article
- Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?Frontiers in pharmacology · 2017Review
- Sphingosine-1-Phosphate Receptor 5 Modulates Early-Stage Processes during Fibrogenesis in a Mouse Model of Systemic Sclerosis: A Pilot Study.Frontiers in immunology · 2017Article
- Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs.Neuromolecular medicine · 2016Review
- Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.British journal of pharmacology · 2016Article
- FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in a mouse model by impairing the motility of bone marrow-derived mesenchymal stem cells.Inflammation · 2014Article
- Dual role of sphingosine kinase-1 in promoting the differentiation of dermal fibroblasts and the dissemination of melanoma cells.Oncogene · 2014Article
- Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
The novel immunomodulator FTY720 is an effective immunosuppressive agent in experimental models of transplantation and autoimmunity and is currently undergoing phase III clinical trials for multiple sclerosis. Phosphorylated FTY720 is a structural analogue of sphingosine 1-phosphate (S1P) and therefore acts as a high-affinity agonist at four of the five G protein-coupled S1P receptors. It has been well established that there exists a crosstalk between S1P and transforming growth factor (TGF)-beta signaling. Because TGF-beta is the most prominent inductor of fibrosis and myofibroblasts are primarily responsible for excessive matrix protein formation, we examined whether FTY720, in analogy to TGF-beta, induces differentiation of fibroblasts into myofibroblasts. Indeed, FTY720 provoked myofibroblast differentiation comparable with that of TGF-beta. For biological efficacy, FTY720 required endogenous phosphorylation because inhibition of sphingosine kinase completely prevented FTY720 from inducing the differentiation process. Moreover, we identified the lysophospholipid receptor S1P3 as the crucial receptor subtype for FTY720-induced myofibroblast differentiation because the effect was abolished in fibroblasts isolated from S1P3 knockout mice. Finally, we determined that downstream of S1P3 signaling Smad3 activation is essential for myofibroblast differentiation in response to FTY720. Thus, FTY720 may have adverse fibrotic effects related to its activity on S1P3 signaling.
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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.