Inhibitory effect of tranilast on activation and transforming growth factor beta 1 expression in cultured rat stellate cells

被引:58
作者
Ikeda, H
Inao, M
Fujiwara, K
机构
[1] SAITAMA MED SCH,DEPT INTERNAL MED 3,MOROYAMA,SAITAMA 35004,JAPAN
[2] UNIV TOKYO,FAC MED,DEPT INTERNAL MED 1,BUNKYO KU,TOKYO 113,JAPAN
关键词
D O I
10.1006/bbrc.1996.1508
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Stellate cells, the primary extracellular matrix-producing cells in the liver, undergo activation characterized by fibrogenesis, proliferation and smooth muscle alpha-actin expression, in hepatic fibrosis or when cultured on plastic. TGF beta 1 is known to have a pivotal role in fibrogenesis. Tranilast, a drug used for allergic diseases with anti-inflammatory effects, is known to inhibit collagen synthesis by cultured fibroblasts. Thus, effects of tranilast on activation and TGF beta 1 expression in stellate cells was investigated in vitro. Tranilast reduced collagen synthesis in a dose-related manner up to 50.8% of the control. This effect was reversible after tranilast withdrawal. The mobility of procollagen on gel electrophoresis and the ratio of intracellular procollagen to extracellular collagen concentrations were not affected by tranilast. Tranilast decreased DNA synthesis and increased smooth muscle cr-actin expression. mRNA expressions of procollagen and TGF beta 1 were reduced by tranilast. Tranilast with anti-fibrogenic and anti-inflammatory actions merits consideration as a candidate for therapeutic agent of hepatic fibrosis. (C) 1996 Academic Press, Inc.
引用
收藏
页码:322 / 327
页数:6
相关论文
共 40 条
[11]   A TECHNIQUE FOR RADIOLABELING DNA RESTRICTION ENDONUCLEASE FRAGMENTS TO HIGH SPECIFIC ACTIVITY [J].
FEINBERG, AP ;
VOGELSTEIN, B .
ANALYTICAL BIOCHEMISTRY, 1983, 132 (01) :6-13
[12]  
FRIEDMAN SL, 1993, NEW ENGL J MED, V328, P1828
[13]   ACTIVATION OF CULTURED RAT HEPATIC LIPOCYTES BY KUPFFER CELL CONDITIONED MEDIUM - DIRECT ENHANCEMENT OF MATRIX SYNTHESIS AND STIMULATION OF CELL-PROLIFERATION VIA INDUCTION OF PLATELET-DERIVED GROWTH-FACTOR RECEPTORS [J].
FRIEDMAN, SL ;
ARTHUR, MJP .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (06) :1780-1785
[14]  
FRIEDMAN SL, 1989, J BIOL CHEM, V264, P10756
[15]   ISOLATION AND CULTURE OF HEPATIC LIPOCYTES, KUPFFER CELLS, AND SINUSOIDAL ENDOTHELIAL-CELLS BY DENSITY GRADIENT CENTRIFUGATION WITH STRACTAN [J].
FRIEDMAN, SL ;
ROLL, FJ .
ANALYTICAL BIOCHEMISTRY, 1987, 161 (01) :207-218
[16]   TISSUE DISTRIBUTION, QUANTITATION AND PROLIFERATION KINETICS OF FAT-STORING CELLS IN CARBON TETRACHLORIDE-INJURED RAT-LIVER [J].
GEERTS, A ;
LAZOU, JM ;
DEBLESER, P ;
WISSE, E .
HEPATOLOGY, 1991, 13 (06) :1193-1202
[17]   CYCLOSPORINE-A AND FK-506 IN INHIBITION OF RAT ITO CELL ACTIVATION IN-VITRO [J].
IKEDA, H ;
FUJIWARA, K .
HEPATOLOGY, 1995, 21 (04) :1161-1166
[18]  
ISAJI M, 1994, LIFE SCI, V55, P287
[19]   AUTOCRINE SECRETION OF TRANSFORMING GROWTH-FACTOR-BETA IN CULTURED RAT MESANGIAL CELLS [J].
KANAME, S ;
UCHIDA, S ;
OGATA, E ;
KUROKAWA, K .
KIDNEY INTERNATIONAL, 1992, 42 (06) :1319-1327
[20]   FAT-STORING CELLS OF THE RAT-LIVER - THEIR ISOLATION AND PURIFICATION [J].
KNOOK, DL ;
SEFFELAAR, AM ;
DELEEUW, AM .
EXPERIMENTAL CELL RESEARCH, 1982, 139 (02) :468-471