Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

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.

[img]
Preview
Published Version
PDF
3MB

View at publisher

Abstract

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.

Citations

60 citations in Web of Science®
66 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

169 downloads since deposited on 23 May 2011
94 downloads since 12 months

Detailed statistics

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
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:23 May 2011 14:26
Last Modified:17 Jul 2014 03:17
Publisher:Rockefeller University Press
ISSN:0022-1007
Additional Information:Copyright: the Authors
Publisher DOI:10.1084/jem.20101629
PubMed ID:21518801

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page