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Journal articles
Platelet-derived serotonin links vascular disease and tissue fibrosis.: Serotonin in 5-HT2B fibrotic disease
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.
Cited literature [50 references]
https://www.hal.inserm.fr/inserm-00589662
Contributor : Luc Maroteaux <>
Submitted on : Saturday, October 29, 2011 - 7:00:04 AM
Last modification on : Wednesday, February 24, 2021 - 12:32:02 PM
Long-term archiving on: : Saturday, December 3, 2016 - 9:24:14 AM
Contributor : Luc Maroteaux <>
Submitted on : Saturday, October 29, 2011 - 7:00:04 AM
Last modification on : Wednesday, February 24, 2021 - 12:32:02 PM
Long-term archiving on: : Saturday, December 3, 2016 - 9:24:14 AM
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JEM_20101629_0_s_22_LM.pdf
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