Transforming growth factor-β-induced stimulation of formation of collagen fiber network and anti-fibrotic effect of taurine in an in vitro model of hepatic fibrosis

被引:29
作者
Kato, J
Ido, A
Hasuike, S
Uto, H
Hori, T
Hayashi, K
Murakami, S
Terano, A
Tsubouchi, H
机构
[1] Miyazaki Univ, Fac Med, Dept Internal Med 2, Kiyotake, Miyazaki 8891692, Japan
[2] Kyoto Univ Hosp, Translat Res Ctr, Dept Expt Therapeut, Sakyo Ku, Kyoto 6068507, Japan
[3] Taisho Pharmaceut Co Ltd, Med Res Labs, Kita Ku, Saitama 3319530, Japan
[4] Dokkyo Univ, Sch Med, Dept Gastroenterol, Shimotsuga, Tochigi 3210293, Japan
关键词
M cell; hepatic stellate cell; myofibroblast; liver cirrhosis; procollagen alpha 1(I);
D O I
10.1016/j.hepres.2004.04.006
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 (1 ng/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 (10-50 mM), 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. (C) 2004 Elsevier B.V. All rights reserved.
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页码:34 / 41
页数:8
相关论文
共 34 条
[1]
Inhibitory effect of heparin on collagen fiber formation in hepatic cells in culture [J].
Akimoto, K ;
Ikeda, M ;
Sorimachi, K .
CELL STRUCTURE AND FUNCTION, 1997, 22 (05) :533-538
[2]
NUCLEOTIDE-SEQUENCES OF COMPLEMENTARY DEOXYRIBONUCLEIC ACIDS FOR THE PRO-ALPHA-1 CHAIN OF HUMAN TYPE-I PROCOLLAGEN - STATISTICAL EVALUATION OF STRUCTURES THAT ARE CONSERVED DURING EVOLUTION [J].
BERNARD, MP ;
CHU, ML ;
MYERS, JC ;
RAMIREZ, F ;
EIKENBERRY, EF ;
PROCKOP, DJ .
BIOCHEMISTRY, 1983, 22 (22) :5213-5223
[3]
Chronic liver injury, TGF-β, and cancer [J].
Bissell, DM .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2001, 33 (04) :179-190
[4]
Edamoto Y, 1996, CANCER, V77, P1787
[5]
Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury [J].
Friedman, SL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) :2247-2250
[6]
Sp1 is required for the early response of alpha 2(I) collagen to transforming growth factor-beta 1 [J].
Greenwel, P ;
Inagaki, Y ;
Hu, W ;
Walsh, M ;
Ramirez, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (32) :19738-19745
[7]
Roles of TGF-beta in hepatic fibrosis [J].
Gressner, AM ;
Weiskirchen, R ;
Breitkopf, K ;
Dooley, S .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2002, 7 :D793-D807
[8]
Regulation of transforming growth factor-β1 mRNA expression by taurine and niacin in the bleomycin hamster model of lung fibrosis [J].
Gurujeyalakshmi, G ;
Hollinger, MA ;
Giri, SN .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1998, 18 (03) :334-342
[9]
Gurujeyalakshmi G, 2000, J PHARMACOL EXP THER, V293, P82
[10]
DEVELOPMENTAL EXPRESSION OF 4 NOVEL SERINE THREONINE KINASE RECEPTORS HOMOLOGOUS TO THE ACTIVIN TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR FAMILY [J].
HE, WW ;
GUSTAFSON, ML ;
HIROBE, S ;
DONAHOE, PK .
DEVELOPMENTAL DYNAMICS, 1993, 196 (02) :133-142