Platelet-derived serotonin links vascular disease and tissue fibrosis. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Experimental Medicine Year : 2011

Platelet-derived serotonin links vascular disease and tissue fibrosis.

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.
Fichier principal
Vignette du fichier
JEM_20101629_0_s_22_LM.pdf (4.98 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

inserm-00589662 , version 1 (29-10-2011)

Identifiers

Cite

Clara Dees, Alfiya Akhmetshina, Pawel Zerr, Nicole Reich, Katrin Palumbo, et al.. Platelet-derived serotonin links vascular disease and tissue fibrosis.: Serotonin in 5-HT2B fibrotic disease. Journal of Experimental Medicine, 2011, 208 (5), pp.961-972. ⟨10.1084/jem.20101629⟩. ⟨inserm-00589662⟩
709 View
792 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More