Bleomycin increases steady-state levels of type I collagen, fibronectin and decorin mRNAs in human skin fibroblasts.

Abstract

Bleomycin is a drug capable of inducing tissue fibrosis. In this study, the effects of bleomycin on gene expression of extracellular matrix encoding alpha1(I) collagen, fibronectin and decorin were determined in vitro in human dermal fibroblasts. Northern blot analysis showed that bleomycin upregulated alpha(I) collagen, fibronectin and decorin gene expression dose-dependently between 1 nM and 1 microM. Bleomycin at 100 nM upregulated alpha1(I) collagen, fibronectin and decorin mRNA expression with a peak at 6 h following stimulation in normal skin fibroblast monolayers. Bleomycin enhanced mRNA expression encoding these extracellular matrix proteins in both normal dermal and scleroderma fibroblasts. Concomitant stimulation with bleomycin and interferon-gamma (1,000 U/ml), a representative antifibrotic cytokine, decreased alpha1(I) collagen mRNA expression. Bleomycin also mildly upregulated mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) coordinately in normal skin fibroblasts. Our results indicate that bleomycin modulates gene expression of extracellular matrix proteins in dermal fibroblasts, and this effect may be mediated by TGF-beta and CTGF.