THE EFFECT OF HEPARIN ON CELL-PROLIFERATION AND TYPE-I COLLAGEN-SYNTHESIS BY ADULT HUMAN DERMAL FIBROBLASTS

(1), A commercial heparin inhibited the proliferation of two normal human dermal fibroblast cultures in a dose-responsive manner. 300 mug heparin/ml gave the maximum inhibition of 65%. Proliferation of fibroblasts from a patient with progressive systemic sclerosis was similarly inhibited by heparin. Heparan sulphate, pentosan polysulphate and a fucoidan also inhibited proliferation of the fibroblast cultures but chondroitin sulphate, dermatan sulphate and hyaluronate had no effect. (2), Type-I collagen synthesis per cell was elevated by up to 1.5-fold in the normal fibroblast cultures when proliferation was inhibited by heparin, heparan sulphate, pentosan polysulphate and the fucoidan. Progressive systemic sclerosis fibroblasts synthesized more collagen than the normal cell cultures and this was further stimulated by heparin and pentosan polysulphate. In contrast, heparin and the other polysulphates inhibited type-I collagen synthesis by about 20-30% in normal confluent fibroblast cultures. Collagen synthesis by confluent systemic sclerosis fibroblasts was reduced by only about 10%. (3), Total [S-35]proteoglycan synthesis per cell was greatly elevated (approx. 2.5-fold) in normal subconfluent cultures treated with heparin. In contrast, heparin stimulated only a small increase in [S-35]sulphate incorporation into proteoglycans in confluent cultures.