title: The role of endothelin-1 signaling in the fibrosis observed in systemic sclerosis.
abstract: Scleroderma (systemic sclerosis, SSc) is an autoimmune disease of unknown etiology characterized by organ fibrosis. There is no therapy for SSc. However, a recent body of evidence strongly implicates endothelin-1 (ET-1) in the pathogenesis of SSc. ET-1 is found in abundance in SSc patients. ET-1 directly induces fibrogenic effects in vitro, and is required for the ability of TGFβ to induce fibrogenic effects both in vitro and in vivo. Moreover, endothelin receptor antagonism reverses key features of the persistent fibrotic phenotype of fibroblasts isolated from lesions of SSc patients. However, clinically, endothelin receptor antagonism alone has had mixed results. This minireview summarizes these observations.
authors.affiliation: Department of Dentistry, Dental Sciences Building, University of Western Ontario, London, ON N6A5C1, Canada. andrew.leask@schulich.uwo.ca
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology*; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D012595:Scleroderma, Systemic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D019332:Endothelin-1; D016212:Transforming Growth Factor beta