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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 284 (1993), S. 440-444 
    ISSN: 1432-069X
    Keywords: Tumor necrosis factor-α ; Normal fibroblasts ; Scleroderma fibroblasts ; Connective tissue metabolism ; Gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies have demonstrated that tumor necrosis factor-α(TNF-α) selectively decreases production of collagens I and III, the major types of collagen in the dermis, and increases production of collagenase in cultured dermal fibroblasts. The effects of TNF-α on collagens I, III and VI, fibronectin and collagenase gene expression by fibroblasts derived from normal individuals and patients with systemic sclerosis (SSc) were studied. SSc is characterized by excessive accumulation of collagen in the skin and in certain organs. TNF-α inhibited collagen production and mRNA levels of collagens I and III and of fibronectin, and stimulated collagenase activity and collagenase mRNA levels in SSs fibroblasts. Levels of mRNA for α1(VI) and α3(VI) collagen and for Β-actin were unaltered in SSc fibroblasts incubated with TNF-α. Similar results were observed for mRNA levels in normal fibroblasts incubated with TNF-α. These results suggest that TNF-α could be expected to be beneficial in the treatment of SSc. In addition, our results indicated that collagen-VI expression is regulated independently from expression of collagens I and III, and expression of fibronectin and collagens I and III are regulated in parallel in fibroblasts treated with TNF-α.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-069X
    Keywords: Key words In vitro aging ; Fibroblasts ; Type I collagen ; TGFβ ; TGFβ receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that the expression of type I collagen, the most abundant protein in the dermis, is reduced in in vitro-aging fibroblast cultures, but the mechanism controlling the reduction of type I collagen expression is not understood. Recent studies, however, have demonstrated that transforming growth factor β (TGFβ) plays an important role in the regulation of type I collagen expression. The purpose of this study was to investigate the role of TGFβ in downregulation of type I collagen expression in in vitro-aged fibroblasts. We compared the expression of mRNA for α1(I) collagen, TGFβ ,TGFβ type I receptor and TGFβ type II receptor in early- and late-passage fibroblasts by Northern blot hybridizations. The mRNA levels of α1(I) collagen, TGFβ, and TGFβ receptors I and II in late-passage fibroblasts were reduced to 62%, 62%, 59% and 59%, respectively, of those in early-passage fibroblasts. We also compared TGFβ receptor binding in early- and late-passage fibroblasts using receptor binding assays. The affinity of   125 I-TGFβ in late-passage fibroblasts was lower than that in early-passage fibroblasts. These results suggest that the reduction of type I collagen expression in in vitro-aged fibroblasts is regulated by reduced expression of TGFβ and TGFβ receptors I and II and by decreased TGFβ receptor binding ability of the fibroblasts.
    Type of Medium: Electronic Resource
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