Role of transforming growth factor-β₁ in fibroblasts derived from normal and hypertrophic scarred skin

Abstract

In order to elucidate the effect of transforming growth factor beta ₁ (TGF-β ₁ ) on normal dermal fibroblasts (NDF) and on fibroblasts derived from hypertrophic scar (HSF) tissue, we compared proliferation, the levels of TGF-β ₁ protein and mRNA, the activity of type-I collagen synthesis and collagenase, and the response to recombinant human (rh) TGF-β ₁ in cultures of both types of cells which had been simultaneously collected from the same patients. We also studied the effects of anti-TGF-β ₁ antibody on the proliferation of these two types of fibroblasts in culture. In spite of the fact that the growth rate of HSF was higher than that of NDF, NDF proliferation was more sensitive to the concentration of rhTGF-β ₁ . With respect to rates of synthesis, the results obtained in both groups revealed that the production of type-I collagen was higher and collagenase activity was lower in culture supernatants of HSF. However, the addition of rhTGF-β 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 production of TGF-β ₁ and the expression of TGF-β ₁ mRNA in HSF were greater than in NDF. Furthermore, anti-TGF-β ₁ antibody reduced the rate of growth of HSF. These results suggest that HSF are able to produce TGF-β ₁ , resulting in enhanced proliferation of these cells as well as in a rapid synthesis of type-I collagen through an autocrine mechanism which may lead to hypertrophic scarring.