Elevated pro alpha 2(I) collagen mRNA levels in cultured scleroderma fibroblasts result from an increased transcription rate of the corresponding gene.

Fibroblasts cultured from affected and unaffected skin sites of three scleroderma patients were studied for the activation of type I collagen gene expression. Dot blot hybridizations with pro alpha 2(I) collagen specific cDNA probe revealed 2.9-4.8-fold increases in pro alpha 2(I) mRNA levels in the affected fibroblasts over the unaffected control cells. Transcription rate of the pro alpha 2(I) gene in the nuclei isolated from the same cells was 2.0-3.7-fold higher in the scleroderma fibroblasts than in the controls. The results show that scleroderma fibroblasts have undergone activation of collagen gene expression at the transcriptional level, which subsequently results in elevated procollagen mRNA levels, overproduction of collagen, and development of dermal fibrosis.