Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat

We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-bet a receptor (AdCAT beta-TR) in the liver of rats treated with dimethylnitros amine, a model of persistent liver fibrosis. In rats that received a single application of AdCAT beta-TR via the portal vein, liver fibrosis as assess ed by histology and hydroxyproline content was markedly attenuated. All AdC AT beta-TR-treated rats remained alive, and their serum levels of hyaluroni c acid and transaminases remained at low levels, whereas all the AdCAT beta -TR-untreated rats died of liver dysfunction. The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearl y in a persistent fibrosis model that prevention of fibrosis by anti-TGF-be ta intervention could he therapeutically useful.