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.
Oi
Mieko
M
Department of Environmental Immunodermatology, Tokyo Medical and Dental University, Post Graduate School, Japan. BYG03573@nifty.ne.jp
Yamamoto
Toshiyuki
T
Nishioka
Kiyoshi
K
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects*; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005856:Germ-Free Life; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D003094:Collagen