DISTINCT PATTERNS OF COLLAGEN GENE-EXPRESSION ARE SEEN IN NORMAL AND KELOID FIBROBLASTS GROWN IN 3-DIMENSIONAL CULTURE

The purpose of this study was to examine collagen gene expression in v arious types of scar fibroblasts as well as normal fibroblasts tn a no vel three-dimensional culture system and to compare them with those in a monolayer culture system. Cells in three-dimensional culture formed multiple layers within the self-produced dense extracellular matrix a nd formed a dermis-like structure. In monolayer culture, both normal a nd scar fibroblasts continued to express high levels of mRNA for pro a lpha 1(I) and pro alpha 1(III) collagens. However, in three-dimensiona l culture, the mRNA levels gradually declined in normal fibroblasts. I n contrast, mRNA levels remained high in keloid and hypertrophic scar fibroblasts. Atrophic scar fibroblasts demonstrated similar changes to normal fibroblasts in three-dimensional culture. When we compared mRN A expression in fibroblasts from the centre and the edge of hypertroph ic scar cells from the centre showed a persistently decreased level of collagenase mRNA expression. These results suggest that the mRNA expr ession pattern of pro alpha 1(I) and pro alpha 1(UI) collagens varies depending on the culture system. Fibroblasts from keloids and hypertro phic scar may have a defective system of down-regulation in extracellu lar matrix metabolism.