Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?
Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors,...
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| Format: | Article |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00296/full |
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| author | Ambra Vestri Federica Pierucci Federica Pierucci Alessia Frati Lucia Monaco Elisabetta Meacci Elisabetta Meacci |
| author_facet | Ambra Vestri Federica Pierucci Federica Pierucci Alessia Frati Lucia Monaco Elisabetta Meacci Elisabetta Meacci |
| author_sort | Ambra Vestri |
| collection | DOAJ |
| description | Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system. There is accumulating evidence for the important role of S1P as a mediator of many processes, such as angiogenesis, carcinogenesis and immunity, and, ultimately, fibrosis. After a tissue injury, the imbalance between the production of extracellular matrix (ECM) and its degradation, which occurs due to chronic inflammatory conditions, leads to an accumulation of ECM and, consequential, organ dysfunction. In these pathological conditions, many factors have been described to act as pro- and anti-fibrotic agents, including S1P. This bioactive lipid exhibits both pro- and anti-fibrotic effects, depending on its site of action. In this review, after a brief description of sphingolipid metabolism and signaling, we emphasize the involvement of the S1P/S1PR axis and the downstream signaling pathways in the development of fibrosis. The current knowledge of the therapeutic potential of S1PR subtype modulators in the treatment of the cardiac functions and fibrinogenesis are also examined. |
| first_indexed | 2024-04-14T05:15:59Z |
| format | Article |
| id | doaj.art-f872df4f18ff452fafe2d8f63b1a4dfd |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T05:15:59Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f872df4f18ff452fafe2d8f63b1a4dfd2022-12-22T02:10:22ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-06-01810.3389/fphar.2017.00296265250Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?Ambra Vestri0Federica Pierucci1Federica Pierucci2Alessia Frati3Lucia Monaco4Elisabetta Meacci5Elisabetta Meacci6Department of Experimental and Clinical Biomedical Sciences “Mario Serio", Molecular and Applied Biology Research Unit, University of FlorenceFlorence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio", Molecular and Applied Biology Research Unit, University of FlorenceFlorence, ItalyInteruniversity Institutes of MyologyFirenze, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio", Molecular and Applied Biology Research Unit, University of FlorenceFlorence, ItalyDepartment of Physiology and Pharmacology “Vittorio Erspamer", Sapienza University of RomeRome, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio", Molecular and Applied Biology Research Unit, University of FlorenceFlorence, ItalyInteruniversity Institutes of MyologyFirenze, ItalySphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system. There is accumulating evidence for the important role of S1P as a mediator of many processes, such as angiogenesis, carcinogenesis and immunity, and, ultimately, fibrosis. After a tissue injury, the imbalance between the production of extracellular matrix (ECM) and its degradation, which occurs due to chronic inflammatory conditions, leads to an accumulation of ECM and, consequential, organ dysfunction. In these pathological conditions, many factors have been described to act as pro- and anti-fibrotic agents, including S1P. This bioactive lipid exhibits both pro- and anti-fibrotic effects, depending on its site of action. In this review, after a brief description of sphingolipid metabolism and signaling, we emphasize the involvement of the S1P/S1PR axis and the downstream signaling pathways in the development of fibrosis. The current knowledge of the therapeutic potential of S1PR subtype modulators in the treatment of the cardiac functions and fibrinogenesis are also examined.http://journal.frontiersin.org/article/10.3389/fphar.2017.00296/fullsphingosine 1-phosphatesphingolipidsmatrix metalloproteinasescardiomyocytescollagen accumulationG-coupled receptor |
| spellingShingle | Ambra Vestri Federica Pierucci Federica Pierucci Alessia Frati Lucia Monaco Elisabetta Meacci Elisabetta Meacci Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis? Frontiers in Pharmacology sphingosine 1-phosphate sphingolipids matrix metalloproteinases cardiomyocytes collagen accumulation G-coupled receptor |
| title | Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis? |
| title_full | Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis? |
| title_fullStr | Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis? |
| title_full_unstemmed | Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis? |
| title_short | Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis? |
| title_sort | sphingosine 1 phosphate receptors do they have a therapeutic potential in cardiac fibrosis |
| topic | sphingosine 1-phosphate sphingolipids matrix metalloproteinases cardiomyocytes collagen accumulation G-coupled receptor |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00296/full |
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