Regulation of collagen gene expression in keloids and hypertrophic scars

Abstract

The synthesis of type I and III collagens in cultured skin fibroblasts from normal skin, normal scar, hypertrophic scar, and keloids was examined. The ratio of type I/III collagen was significantly elevated in keloids compared to that in the other groups. When mRNA steady-state levels coding for alpha 1(I) procollagen were determined, it was apparent that this increase in the type I/III collagen ratio in keloids was paralleled by a specific increase in alpha 1(I) procollagen mRNA. This specific increase in alpha 1(I) procollagen mRNA in keloids was the result of increased gene expression because the transcription rate of the alpha 1(I) procollagen gene was significantly elevated in keloids, as determined by nuclear runoff transcription. The rate of transcription of the alpha 1(I) procollagen gene was also elevated in hypertrophic scars, although no concomitant increase in alpha 1(I) procollagen mRNA levels or alteration in the type I/III collagen ratio was observed. These data indicate that the rate of gene transcription of alpha 1(I) procollagen is increased in both hypertrophic scars and keloids, but only keloids exhibit increased steady-state levels of alpha 1(I) procollagen mRNA and concurrent increases in type I collagen. These results suggest that at least two distinct mechanisms, one pretranscriptional and one post-transcriptional, regulate type I collagen synthesis. It is possible, therefore, that in keloids, neither mechanism functions efficiently to down-regulate type I collagen. In hypertrophic scars, however, the post-transcriptional mechanisms are able to decrease elevated levels of mRNA coding for alpha 1(I) procollagen that result from increased transcription of the alpha 1(I) procollagen gene.