Connective tissue metabolism including cytokines in scleroderma.
Fibroblasts within the skin of scleroderma patients constitute a phenotypically heterogeneous population with regard to expression of collagens, cytokines, and cytokine receptors. By in situ hybridization techniques, scleroderma skin is shown to contain a subpopulation of fibroblasts that are stimulated for expression of type VI collagen; the size of this subpopulation is larger than that found in normal skin. The heterogeneity in collagen production among scleroderma fibroblasts can also be demonstrated in vitro following sorting by flow cytometric analysis. An isoform of a cytokine known to be a potent modulator of collagen expression, transforming growth factor-beta 2, is overexpressed in and around inflammatory infiltrates in biopsies of skin from scleroderma patients. Scleroderma fibroblasts grown in culture express slightly elevated levels of transcripts for transforming growth factor-beta 1, demonstrated by Northern analysis. Osteonectin, or SPARC (secreted protein, acidic and rich in cysteine), messenger RNA is also clearly elevated in fibroblasts cultured from the affected skin of scleroderma patients. The affinity of epidermal growth factor receptors on fibroblasts derived from the skin of scleroderma patients is decreased compared with that of receptors on normal fibroblasts. Platelet-derived growth factor-beta receptors were detectable by immunohistochemical staining in dermal vessels and surrounding fibroblasts in 13 of 14 biopsies of skin of scleroderma patients, whereas they were absent in sections of normal skin. These studies completed within the past year allow recognition of the importance of interactions between cell types, and the possible consequences of alterations in cytokine secretory patterns and cell responsiveness.
Unemori
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Genentech, Inc., South San Francisco, California.
Amento
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D003240:Connective Tissue Diseases / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000503:physiopathology
D016207:Cytokines