Scleroderma is an intricate disorder of unknown etiology. In efforts to unravel the underlying mechanisms involved in the pathogenesis of scleroderma, we propose to investigate the molecular basis of extracellular matrix abnormalities and endothelial dysfunction. Extracellular matrix is composed of a plethora of macromolecules with defined structural and biological activities. Components of extracellular matrix can bind to and modulate the activity of an array of growth factors and cytokines leading to fibrosis. In this application, matrix biosynthesis and remodeling in tight skin (Tsk2+) mice, an animal model of scleroderma, will be examined. RELEVANCE: This project examines the roles of abnormal collagen accumulation and enhanced stability in the development of fibrosis associated with scleroderma. [unreadable] [unreadable] [unreadable]