Inhibitory effect of tranilast on activation and transforming growth factor beta 1 expression in cultured rat stellate cells.
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 alpha-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.
Ikeda
H
H
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Inao
M
M
Fujiwara
K
K
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D015342:DNA Probes; D005109:Extracellular Matrix; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011347:Procollagen / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D015342:DNA Probes; D006634:Histamine H1 Antagonists; D011347:Procollagen; D016212:Transforming Growth Factor beta; D062367:ortho-Aminobenzoates; D003094:Collagen; D004247:DNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C012293:tranilast