A FIBROBLAST CELL-LINE CULTURED FROM A HYPERTROPHIC SCAR DISPLAYS SELECTIVE DOWN-REGULATION OF COLLAGEN GENE-EXPRESSION - BARELY DETECTABLEMESSENGER-RNA LEVELS OF THE PRO-ALPHA-1(III) CHAIN OF TYPE-III COLLAGEN

The present study was designed to investigate the expression of type I , III and VI collagens by a fibroblast cell line initiated from a hype rtrophic scar, The same tissue has previously been demonstrated to dis play markedly elevated expression of type I and III collagen mRNAs in vivo. Unexpectedly, slot-blot and Northern hybridizations revealed a b arely detectable steady-state level of pro alpha 1(III) collagen chain mRNA in cultured hypertrophic scar fibroblasts. The levels of pro alp ha 1(I) and alpha 2(VI) collagen chain mRNAs mere essentially the same in fibroblasts cultured from hypertrophic scar and in fibroblasts cul tured from normal skin, However, Northern blot analyses indicated that the ratio of 5.8 kb to 4.8 kb species of pro alpha 1(I) collagen mRNA was slightly reduced in fibroblasts originating from the hypertrophic scar compared to that in normal fibroblasts. When normal fibroblasts were incubated in conditioned medium from hypertrophic scar cultures, the expression of pro alpha 1(III) collagen chain mRNA decreased to a markedly lower level, Our studies suggest that collagen synthesis by f ibroblasts in hypertrophic scars is stimulated by humoral factors whic h are active only in vivo. Furthermore, the results suggest that fibro blasts cultured from hypertrophic scar display a selective downregulat ion of different collagen genes and that this downregulation is exerte d through an autocrine mechanism.