Coordinated regulation of type I and type III collagen production and mRNA levels of pro alpha 1(I) and pro alpha 2(I) collagen in cultured morphea fibroblasts

Abstract

Fibroblast cultures were started from affected and unaffected skin areas of six patients with localized scleroderma in an active stage. The cell lines were studied for synthesis of procollagens and fibronectin by metabolic labeling with 3H-proline and for their contents of mRNAs for pro alpha 1(I) and pro alpha 2(I) collagen. For this purpose a cDNA clone for human pro alpha 1(I) collagen mRNA was constructed. The clone was identified by restriction site mapping and hybridization to the specific mRNAs. All the scleroderma fibroblast lines produced increased amounts of type I and type III collagens and fibronectin during the early passages. The cell lines gradually reduced their elevated synthesis of collagen and fibronectin to normal or near normal levels by the tenth passage. The ratios of alpha 1(I) and alpha 2(I) chains and of type I and type III collagens, and the extent of type I procollagen processing, remained relatively unchanged in all the cultures. The cellular levels of type I procollagen mRNAs were increased in all the cells exhibiting an increased synthesis of collagen. The results suggest that in localized scleroderma the fibroblasts have undergone a coordinated activation of collagen synthesis at transcriptional level.