Inhibitory Effect of Tranilast on Activation and Transforming Growth Factor β1 Expression in Cultured Rat Stellate Cells

Abstract

Stellate cells, the primary extracellular matrix-producing cells in the liver, undergo activation characterized by fibrogenesis, proliferation and smooth muscle α-actin expression, in hepatic fibrosis or when cultured on plastic. TGFβ1 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 TGFβ1 expression in stellate cells was investigatedin 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 α-actin expression. mRNA expressions of procollagen and TGFβ1 were reduced by tranilast. Tranilast with anti-fibrogenic and anti-inflammatory actions merits consideration as a candidate for therapeutic agent of hepatic fibrosis.