Platelet-derived serotonin links vascular disease and tissue fibrosis
Clara Dees1, Alfiya Akhmetshina, Pawel Zerr
1Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
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.
Related Concept Videos
Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
Intracellular Signaling Affects Focal Adhesions
Some...
Clot Retraction and Fibrinolysis
Vascular Spasm
Paracrine Signaling
Anticoagulant Drugs: Low-Molecular-Weight Heparins


