Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells
✍ Scribed by Hiroshi Sugawara; Takato Ueno; Takuji Torimura; Sadataka Inuzuka; Kyuichi Tanikawa
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 415 KB
- Volume
- 174
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 [ 3 H]thymidine were investigated in the presence and absence of interleukin-1b (IL-1b). IL-1b significantly increased the uptake of [ 3 H]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-1b, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [ 3 H]-hydroxyproline in the presence and absence of transforming growth factor-b1 (TGF-b1). TGF-b1 significantly increased the production of [ 3 H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca 2/ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP 3 ) in the HSCs. IL-1b induced the increase of intracellular Ca 2/ and IP 3 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.