Inhibitory effect of OPC-15161, a component of fungus Thielavia minor,on proliferation and extracellular matrix production of rat cultured hepatic stellate cells

A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of ³H]thymidine were investigated in the presence and absence of interleukin-1β (IL-1β). IL-1β significantly increased the uptake of ³H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1β, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of ³H]-hydroxyproline in the presence and absence of transforming growth factor-β1 (TGF-β1). TGF-β1 significantly increased the production of ³H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca²⁺ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP₃) in the HSCs. IL-1β induced the increase of intracellular Ca²⁺ and IP₃ concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-15161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo. J. Cell. Physiol. 174:398–406, 1998. © 1998 Wiley-Liss, Inc.