The pathogenesis of systemic sclerosis.
Systemic sclerosis (scleroderma) is a generalized disease of the interstitial connective tissue of several organs characterized by vascular and microvascular injury and fibroblast activation leading to fibrosis. Cell culture models have been instructive in attempts to study the pathogenesis of this disorder. The scleroderma fibroblast in vitro demonstrates persistent, excessive extracellular matrix production, as well as an autocrine abnormality in cell growth regulation with persistent expression of the proto-oncogene c-myc. Since it has not yet been possible to culture scleroderma endothelial cells, human umbilical endothelial cells have been studied with regard to potential informational molecules (peptide regulatory factors, cytokines, growth factors) which selectively injure or alter the function of the endothelium. Transforming growth factor beta and tumor necrosis factor are two of these molecules which are currently under study.
LeRoy
E C
EC
Department of Medicine, Medical University of South Carolina, Charleston, 29425.
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000503:physiopathology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D000090063:Proto-Oncogene Mas; D012595:Scleroderma, Systemic / Q000209:etiology*