KELOID FIBROBLASTS EXHIBIT AN ALTERED RESPONSE TO TGF-BETA

Treatment with transforming growth factor beta1 (TGF-beta1) results in stimulation of total protein synthesis in normal dermal fibroblasts but not in keloid fibroblasts. suggesting that the TGF-beta regulatory program is altered in keloid fibroblasts. However, both keloid and normal fibroblasts treated with TFG-beta1 exhibit accelerated fibronectin biosynthesis, indicating that keloid cells can respond to TGF-beta1. In the absence of serum, the TGF-beta1 - induced increase in fibronectin biosynthesis occurs more rapidly in keloid fibroblasts, also suggesting modification of this regulatory pathway. The TGF-beta1 - mediated increase in keloid fibronectin production is independent of the steroid regulatory pathway for fibronectin, which accelerates synthesis by means of a post-transcriptional mechanism. Thus, TGF-beta1 stimulation of fibronectin production in keloid cells is likely to involve a transcriptional mechanism and keloid overproduction of extracellular matrix components may be due to an inherent modification of the TGF-beta regulatory program.