Fibroblasts from post-burn 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 synthesize the small proteoglycan decorin was assessed by quantitative Western blot analysis of conditioned medium collected from confluent cultures. Levels of mRNA for decorin were assessed by quantitative Northern analysis. Since transforming growth factor-beta 1 is implicated in various fibrotic conditions, including post-burn hypertrophic scar, its effect on decorin synthesis by these paired fibroblast cell strains was assessed. 2. Production of decorin was lower in all cell strains of hypertrophic scar fibroblasts tested, compared with normal dermal fibroblasts 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 significantly different. Four pairs of cell strains were examined at more than one passage and the differences in decorin protein were found to be phenotypically persistent. Treatment of confluent cultures with transforming 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 increase in the length of the dermatan sulphate chain on decorin, a previously reported characteristic of this glycosaminoglycan in hypertrophic scar, was seen in all but two of the strains treated with transforming growth factor-beta 1. The depression of decorin synthesis by transforming growth factor-beta 1 was reversed on removal of the agent and passaging the fibroblasts. 3. The reduced capacity of fibroblasts in hypertrophic scar tissue to synthesize decorin may have implications for the development of the condition since this small proteoglycan is involved in tissue organization and may also play a role in modulating the activity in vivo of fibrogenic cytokines such as transforming growth factor-beta 1.
Scott
P G
PG
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Dodd
C M
CM
Ghahary
A
A
Shen
Y J
YJ
Tredget
E E
EE
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D015153:Blotting, Western; D002056:Burns / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017439:Cicatrix, Hypertrophic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta