Comparison of the Effects of Retinoids and Glucocorticosteroid on Protein and Type IV Collagen Synthesis in HT-1080 (Human Basement Membrane Forming Fibrosarcoma) Cells

Abstract

The effects of various retinoids and dexamethasone on protein and type IV collagen synthesis were studied in human basement membrane-forming fibrosarcoma (HT-1080) cells. Retinol, etretinate (Ro-10-9359), free acid of etretinate (Ro-10-1670) and 13-cis-retinoic acid (RA) in 10(-7) M concentrations slightly reduced total protein and type IV collagen synthesis in the HT-1080 cells, the largest decrease being found with Ro-10-1670 and 13-cis-RA. In contrast, dexamethasone markedly stimulated the incorporation of [14C]proline and the synthesis of [14C]hydroxyproline, an index of the synthesis of type IV collagen. Part of the increase noted in total protein synthesis and type IV collagen synthesis after dexamethasone was due to enhanced intracellular activity of proline. Retinoids did not markedly affect the specific activity of proline. The addition of 13-cis-RA with dexamethasone also increased total protein and type IV collagen synthesis, but to a lesser extent than did dexamethasone alone. 13-cis-RA did not affect the synthesis of fibronectin, a component of connective tissue matrix, while dexamethasone clearly increased the absolute and relative synthesis of fibronectin. Thus the results indicate that retinoids modulate the metabolism of HT-1080 cells, in a way which is separate from that of glucocorticoids. It is also possible that retinoids used in vivo in clinical practice may modulate the metabolism of the connective tissue matrix of basement membranes, i.e. type IV collagen.