Platelet-derived serotonin links vascular disease and tissue fibrosis
- Dees, Clara Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Akhmetshina, Alfiya Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Zerr, Pawel Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Reich, Nicole Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Palumbo, Katrin Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Horn, Angelika Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Jüngel, Astrid Center of Experimental Rheumatology, Zurich Center of Integrative Human Physiology, University Hospital Zurich, 8091 Zurich, Switzerland
- Beyer, Christian Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Krönke, Gerhard Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Zwerina, Jochen Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Reiter, Rudolf ErgoNex Pharma GmbH, CH-9050 Appenzell, Switzerland
- Alenina, Natalia Max Delbrück Center for Molecular Medicine Berlin-Buch, 13092 Berlin, Germany
- Maroteaux, Luc Institut National de la Santé et de la Recherche Médicale Unité 839, Institut du Fer a Moulin, 75005 Paris, France
- Gay, Steffen Center of Experimental Rheumatology, Zurich Center of Integrative Human Physiology, University Hospital Zurich, 8091 Zurich, Switzerland
- Schett, Georg Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- Distler, Oliver Center of Experimental Rheumatology, Zurich Center of Integrative Human Physiology, University Hospital Zurich, 8091 Zurich, Switzerland
- Distler, Jörg H.W. Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
- 2011-4-25
Published in:
- Journal of Experimental Medicine. - Rockefeller University Press. - 2011, vol. 208, no. 5, p. 961-972
English
Vascular damage and platelet activation are associated with tissue remodeling in diseases such as systemic sclerosis, but the molecular mechanisms underlying this association have not been identified. In this study, we show that serotonin (5-hydroxytryptamine [5-HT]) stored in platelets strongly induces extracellular matrix synthesis in interstitial fibroblasts via activation of 5-HT2B receptors (5-HT2B) in a transforming growth factor β (TGF-β)–dependent manner. Dermal fibrosis was reduced in 5-HT2B−/− mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT2B also effectively prevented the onset of experimental fibrosis and ameliorated established fibrosis. Moreover, inhibition of platelet activation prevented fibrosis in different models of skin fibrosis. Consistently, mice deficient for TPH1, the rate-limiting enzyme for 5-HT production outside the central nervous system, showed reduced experimental skin fibrosis. These findings suggest that 5-HT/5-HT2B signaling links vascular damage and platelet activation to tissue remodeling and identify 5-HT2B as a novel therapeutic target to treat fibrotic diseases.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1084/jem.20101629
- ISSN 1540-9538
- Persistent URL
- https://sonar.ch/global/documents/23157
Statistics
Document views: 21
File downloads:
- Full-text: 0