FIBROBLASTS FROM POSTBURN HYPERTROPHIC SCAR TISSUE SYNTHESIZE LESS DECORIN THAN NORMAL DERMAL FIBROBLASTS

1. Fibroblast cultures were established from biopsies of hypertrophic scar and normal dermis taken from nine patients recovering from second - and third-degree burns. The capacity of these fibroblasts to synthes ize the small proteoglycan decorin was assessed by quantitative Wester n blot analysis of conditioned medium collected from confluent culture s. Levels of mRNA for decorin were assessed by quantitative Northern a nalysis, Since transforming growth factor-beta 1 is implicated in vari ous fibrotic conditions, including post-burn hypertrophic scar, its ef fect on decorin synthesis by these paired fibroblast cell strains was assessed. 2. Production of decorin was lower in all cell strains of hy pertrophic scar fibroblasts tested, compared with normal dermal fibrob lasts cultured from the same patients (mean 49 +/- 23 %; P < 0.001, n = 9), Levels of mRNA for decorin were also lower (mean 59 +/- 28 %; P < 0.02, n = 7) but those for biglycan and versican were not significan tly different. Four pairs of cell strains were examined at more than o ne passage and the differences in decorin protein were found to be phe notypically persistent. Treatment of confluent cultures with transform ing growth factor-beta 1 for 3 days caused a reduction in both decorin protein and mRNA in all six strains of hypertrophic scar fibroblasts tested and in five of six strains of normal dermal fibroblasts, An inc rease in the length of the dermatan sulphate chain on decorin, a previ ously reported characteristic of this glycosaminoglycan in hypertrophi c scar, was seen in all but two of the strains treated with transformi ng growth factor-beta 1. The depression of decorin synthesis by transf orming growth factor-beta 1 was reversed on removal of the agent and p assaging the fibroblasts. 3. The reduced capacity of fibroblasts in hy pertrophic scar tissue to synthesize decorin may have implications for the development of the condition since this small proteoglycan is inv olved in tissue organization and may also play a role in modulating th e activity in vivo of fibrogenic cytokines such as transforming growth factor-beta 1.