Role of Rho small GTP binding protein in the regulation of actin cytoskeleton in hepatic stellate cells

Background/Aims: In the fibrotic response to liver injury, hepatic stellate cells are activated, leading to the myofibroblastic cell shape, with actin cytoskeletal reorganization and increased extracellular matrix production. The reorganization of actin cytoskeleton suggests that the small GTP bindi ng protein Rho might modulate the process of this myofibroblastic change. T he aim of this study was to investigate the role of Rho in the phenotypic c hanges of hepatic stellate cells. Methods: The phenotypic changes were inve stigated by the overexpression of Rho regulator, Rho GDI or dominant negati ve mutant of Rho in mouse hepatic stellate cell line, GRX cells. In activat ed rat hepatic stellate cells, the effects of microinjection of Botulinus t oxin C3, which is the specific inhibitor for Rho were analyzed. Furthermore , the effect of C3 on the type I collagen accumulation in hepatic stellate cells was investigated. Results: Overexpression of Rho GDI or the dominant negative mutant of Rho c aused the shrinkage cell shape and suppressed stress fiber formation. Micro injection of toxin C3 caused a markedly distorted cell shape and the disapp earance of stress fibers in rat stellate cells. In addition, C3 strongly su ppressed collagen accumulation in activated stellate cells. Conclusions: These results suggest that Rho regulates the actin cytoskeleta l reorganization, and may be implicated in the collagen accumulation in act ivated stellate cells. These findings provide evidence for the role of Rho in the myofibroblastic phenotype in hepatic stellate cells.