Transforming growth factor-beta-induced stimulation of formation of collagen fiber network and anti-fibrotic effect of taurine in an in vitro model of hepatic fibrosis.
The cell strain M, which was established from normal rat liver cells, is characterized by the active formation of a collagen fiber network. In this study, we investigated the characterization of M cells and evaluated the anti-fibrogenic effects of taurine using this culture system. M cells expressed cytokeratin (CK)8, CK18, vimentin, and alpha-smooth muscle actin, whereas expression of CK-19 or desmin was not detected. Also, M cells expressed transforming growth factor (TGF)-beta1, -beta2, and TGF-beta type I and II receptors, and treatment with TGF-beta1 (1ng/ml) for 6 days markedly stimulated the formation of a collagen fiber network and expression of procollagen alpha1(I) mRNA. When M cells were treated with various concentrations of taurine (10-50mM), network formation and procollagen alpha1(I) expression were significantly suppressed in a dose dependent manner. Additionally, even in the presence of TGF-beta1, taurine treatment effectively reduced the formation of a collagen fiber network. These results suggest that M cells exhibit features of not only hepatocytes but also myofibroblasts, and TGF-beta1 plays an important role in the formation of collagen fiber networks in this culture system. Additionally, this M cell culture system is appropriate for use as an in vitro model of hepatic fibrosis in the evaluation of the anti-fibrogenic effects of various agents.
Kato
Junya
J
Department of Internal Medicine II, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Ido
Akio
A
Hasuike
Satoru
S
Uto
Hirofumi
H
Hori
Takeshi
T
Hayashi
Katsuhiro
K
Murakami
Shigeru
S
Terano
Akira
A
Tsubouchi
Hirohito
H