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

Bleomycin is a drug capable of inducing tissue fibrosis, in this study, the effects of bleomycin on gene expression of extracellular matrix encoding a lpha1(I) collagen, fibronectin and decorin were determined in vitro in huma n dermal fibroblasts, Northern blot analysis showed that bleomycin upregula ted alpha1(I) collagen, fibronectin and decorin gene expression dose-depend ently between 1 nM and 1 muM Bleomycin at 100 nM upregulated alpha1(I) coll agen, fibronectin and decorin mRNA expression with a peak at 6 h following stimulation in normal skin fibroblast monolayers, Bleomycin enhanced mRNA e xpression encoding these extracellular matrix proteins in both normal derma l and scleroderma fibroblasts, Concomitant stimulation with bleomycin and i nterferon-gamma (1000 U/ml), a representative antifibrotic cytokine, decrea sed alpha1(I) collagen mRNA expression. Bleomycin also mildly upregulated m RNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) coordinately in normal skin fibroblasts, Our r esults indicate that bleomycin modulates gene expression of extracellular m atrix proteins in dermal fibroblasts, and this effect mag be mediated by TG F-beta and CTGF.