title: A unifying hypothesis for scleroderma: identifying a target cell for scleroderma.
abstract: We propose that a recent change in the conception of the role of type 1 interferon and the identification of adventitial stem cells suggests a unifying hypothesis for scleroderma. This hypothesis begins with vasospasm. Vasospasm is fully reversible unless, as proposed here, the resulting ischemia leads to apoptosis and activation of type 1 interferon. The interferon, we propose, initiates immune amplification, including characteristic scleroderma-specific antibodies. We propose that the interferon also acts on adventitial stem cells, producing myofibroblasts, rarefaction, and intimal hyperplasia--three morphologic changes that characterize this disease. Regulator of G-protein signaling 5 (RGS5), a regulator of vasoactive G-protein-coupled receptors, is a cell type-specific marker of pericytes and scleroderma myofibroblasts. RGS5 may provide a key link between initial hyperplasia and fibrosis in this disease.
authors.affiliation: Department of Pathology, Center for Cardiovascular Biology, University of Washington School of Medicine, 815 Mercer Street, Seattle, WA 98109, USA. wmahoney@u.washington.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Mahoney
authors.forename: Jo Nadine
authors.initials: JN
authors.lastname: Fleming
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
mesh_terms: D005355:Fibrosis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D020710:RGS Proteins / Q000276:immunology / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D014652:Vascular Diseases / Q000276:immunology* / Q000378:metabolism
chemical_list: D007370:Interferon Type I; D020710:RGS Proteins