Regulation of collagen metabolism and cell growth by epidermal growth factor and ascorbate in cultured human skin fibroblasts.

Epidermal growth factor (2-50 ng/ml), prepared from mouse submaxillary glands, stimulated growth and the synthesis of non-collagenous proteins and hyaluronic acid, but inhibited collagen synthesis in cultured human skin fibroblasts, both stimulation and inhibition being dose-dependent. All these effects may be intrinsic functions of the epidermal growth factor molecule, because these effects were cancelled by the co-presence of antiserum specific for epidermal growth factor and because they were also observed following the addition of human epidermal growth factor produced urogastrone cDNA. On the other hand, L-ascorbate (vitamin C) stimulated growth and collagen synthesis, as well as synthesis of non-collagenous proteins, with no significant effect on hyaluronic acid synthesis. Co-presence of epidermal growth factor and ascorbate gave additive effects on growth and protein synthesis of the cells. These results suggest that the two growth-promoting factors, epidermal growth factor and L-ascorbate, modulate metabolism of extracellular matrix components as well as cell growth in a quite different manner in human skin fibroblasts.