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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-48127

Dees, C; Akhmetshina, A; Zerr, P; Reich, N; Palumbo, K; Horn, A; Jüngel, A; Beyer, C; Krönke, G; Zwerina, J; Reiter, R; Alenina, N; Maroteaux, L; Gay, S; Schett, G; Distler, O; Distler, J H W (2011). Platelet-derived serotonin links vascular disease and tissue fibrosis. Journal of Experimental Medicine, 208(5):961-972.

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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-HT(2B) receptors (5-HT(2B)) in a transforming growth factor β (TGF-β)-dependent manner. Dermal fibrosis was reduced in 5-HT(2B)(-/-) mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT(2B) 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-HT(2B) signaling links vascular damage and platelet activation to tissue remodeling and identify 5-HT(2B) as a novel therapeutic target to treat fibrotic diseases.


79 citations in Web of Science®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:23 May 2011 14:26
Last Modified:17 Jul 2014 03:17
Publisher:Rockefeller University Press
Additional Information:Copyright: the Authors
Publisher DOI:10.1084/jem.20101629
PubMed ID:21518801

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