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

J Hepatol. 2003 Nov;39(5):731-7. doi: 10.1016/s0168-8278(03)00216-2.


Background/aims: Oxidative stress, including the generation of reactive oxygen species (ROS) that acts as a signaling mediator for transforming growth factor (TGF)-beta, plays a key role in hepatic fibrosis. Hepatic stellate cells (HSCs) produce and respond to TGF-beta 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-beta 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-beta inhibition on oxidative stress and the activation of cultured rat HSCs, using the adenovirus-mediated soluble TGF-beta type II receptor.

Results: This soluble receptor secreted from the adenovirus-infected cells binds to TGF-beta. Infection of HSCs with this adenovirus attenuated intracellular levels of TGF-beta1 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-beta receptor may lead to an interruption of the TGF-beta autocrine loop in activated HSC, in part, by inhibiting oxidative stress.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cells, Cultured
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Intracellular Membranes / metabolism
  • Lipid Peroxidation / physiology
  • Liver / cytology
  • Liver / metabolism
  • Liver / physiology*
  • Male
  • NAD / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / physiology
  • Protein Serine-Threonine Kinases
  • RNA, Messenger / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / antagonists & inhibitors
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / chemistry
  • Receptors, Transforming Growth Factor beta / metabolism
  • Receptors, Transforming Growth Factor beta / physiology*
  • Solubility
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1


  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, Transforming Growth Factor beta
  • TGFB1 protein, human
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • NAD
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II