Increased expression of TGF-beta1 in the sclerotic skin in bleomycin-'susceptible' mouse strains.

We previously reported a mouse model for scleroderma by repeated local injections of bleomycin. In this study, we investigated the level of transforming growth factor-beta1 (TGF-beta1) in various mice strains, in order to determine whether the expression of TGF-beta1 correlates with the susceptibility to bleomycin-induced scleroderma. Histological examination revealed prominent dermal sclerosis with increased collagen deposition in the bleomycin-treated skin in B10.A and C3H/HeJ strains as compared with BALB/c, C57BL/6J and DBA/2 strains. Collagen contents in the skin were also increased in B10.A and C3H/HeJ strains. Analysis of skin lesions from B10.A and C3H/HeJ exhibited the increased mRNA expression and protein synthesis of TGF-beta1. TGF-beta1 concentrations in culture supernatants of skin fibroblasts and spleen macrophages were significantly increased by bleomycin stimulation in B10.A and C3H/HeJ strains, and TGF-beta1 gene expression in fibroblasts derived from B10.A and C3H/HeJ strains was significantly increased by bleomycin stimulation. Thus we conclude that C3H/HeJ and B10.A mice are susceptible to bleomycin-induced scleroderma, which may be, in part, due to increased TGF-beta1 gene expression and protein production.