Faculty Bibliography

Transforming growth factor-beta(1) is a well-known and potent biological response modifier that plays an important role in tissue repair and fibrosis. Among the extracellular constituents known to accumulate in fibrotic tissues, glycosaminoglycans are prominent. In this study we examined transforming growth factor-beta(1) synthesis by human dermal fibroblasts derived from both normal and fibrotic cutaneous tissues. We studied the influence of transforming growth factor-beta(1) on glycosaminoglycan synthesis and explored the role of transforming growth factor-beta(1) as an autocrine mediator of its own expression. These investigations are directed at understanding the persistence of the fibrotic phenotype in scarred skin. Transforming growth factor-beta(1) activity was measured by means of a mink lung epithelium growth inhibitory assay. Replicate explants (n = 3) of fibroblasts each derived from normal skin, normal scar, or hypertrophic scar were studied by adding exogenous transforming growth factor-beta(1) at a concentration range of 0 to 10 ng/ml. The resulting conditioned media were removed and assayed for transforming growth factor-beta(1) activity, then the cells were pulsed for an additional 24 hours with radiolabeled glycosaminoglycan precursor, [(3)H]-glucosamine, to evaluate glycosaminoglycan production. Cell-free glycosaminoglycan synthetic profiles were also developed. Transforming growth factor-beta(1) was found to cause a dose-dependent increase in glycosaminoglycan synthesis in hypertrophic scar and normal skin but not in normal scar fibroblasts in cell-mediated glycosaminoglycan synthesis; the reverse was observed in cell-free glycosaminoglycan synthesis, where transforming growth factor-beta(1) increased glycosaminoglycan synthesis in normal scar but not in normal skin or hypertrophic scar. Most endogenous transforming growth factor-beta(1) existed in latent form for normal skin cells but in active form for normal scar and hypertrophic scar fibroblasts