ROLE OF TRANSFORMING GROWTH FACTOR-BETA(1) IN FIBROBLASTS DERIVED FROM NORMAL AND HYPERTROPHIC SCARRED SKIN

In order to elucidate the effect of transforming growth factor beta(1) (TGF-beta(1)) on normal dermal fibroblasts (NDF) and on fibroblasts d erived from hypertrophic scar (HSF) tissue, we compared proliferation, the levels of TGF-beta(1) protein and mRNA, the activity of type-I co llagen synthesis and collagenase, and the response to recombinant huma n (rh) TGF-beta(1) in cultures of both types of cells which had been s imultaneously collected from the same patients, We also studied the ef fects of anti-TGF-beta(1) antibody on the proliferation of these two t ypes of fibroblasts in culture, In spite of the fact that the growth r ate of HSF was higher than that of NDF, NDF proliferation was more sen sitive to the concentration of rhTGF-beta(1). With respect to rates of synthesis, the results obtained in both groups revealed that the prod uction of type-I collagen was higher and collagenase activity was lowe r in culture supernatants of HSE However, the addition of rhTGF-beta(1 ) resulted in a decrease in the collagenase/collagen ratio in NDF, but failed to induce any change in this ratio in HSF. In addition, the pr oduction of TGF-beta(1) and the expression of TGF-beta(1) mRNA in HSF were greater than in NDF. Furthermore, anti-TGF-beta(1) antibody reduc ed the rate of growth of HSF. These results suggest that HSF are able to produce TGF-beta(1), resulting in enhanced proliferation of these c ells as well as in a rapid synthesis of type-I collagen through an aut ocrine mechanism which may lead to hypertrophic scarring.