Inhibitory effect of a soluble transforming growth factor β type II receptor on the activation of rat hepatic stellate cells in primary culture

Background/Aims: Oxidative stress, including the generation of reactive oxygen species (ROS) that acts as a signaling mediator for transforming growth factor (TGF)-β, plays a key role in hepatic fibrosis. Hepatic stellate cells (HSCs) produce and respond to TGF-β in an autocrine manner with increased collagen expression. It has previously been reported that the adenovirus-mediated overexpression of a soluble receptor against the extracellular domain of the TGF-β type II receptor prevents hepatofibrogenesis in vivo, although its inhibitory role and mechanism in HSC activation remains to be elucidated. Methods: In this study, we report on an examination of the actual role of TGF-β inhibition on oxidative stress and the activation of cultured rat HSCs, using the adenovirus-mediated soluble TGF-β type II receptor. Results: This soluble receptor secreted from the adenovirus-infected cells binds to TGF-β. Infection of HSCs with this adenovirus attenuated intracellular levels of TGF-β1 mRNA and protein, NADH oxidative activity, ROS generation and lipid peroxidation, and prevented HSC activation. Conclusions: These findings suggest that this adenovirus-mediated soluble TGF-β receptor may lead to an interruption of the TGF-β autocrine loop in activated HSC, in part, by inhibiting oxidative stress.