Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice

Objective Transforming growth factor beta-1 (TGF-beta1) is thought to be one of the most important factors affecting the development of fibrotic processes in the liver. Aim To discover whether endogenously higher TGF-beta1 production influences the progression and reversibility of liver fibrosis in mice. Method We compared thioacetamide-induced liver fibrosis between wild-type and transgenic mice overexpressing active TGF-beta1 in the liver. Hepatic fibrosis was detected on histological sections, and fibrotic areas were measured by means of morphometric analysis. We also performed Northern blot hybridisation and gelatine zymography to improve our understanding of the process. Results The fibrotic process was faster in the transgenic animals, and regression after the withdrawal of the fibrogenic agent was slower. Fibrosis did not disappear completely from the TGF-beta1 overexpressing mice, even at the endpoint of the experiment. Conclusion Since the increased TGF-beta1 production in the liver slowed down the regression of the liver fibrosis, the behaviour of these transgenic mice is more similar to the human situation, where cirrhosis is irreversible. We propose that this transgenic model is more suitable for investigating fibrotic liver diseases than the experiments done previously on wild-type rodents. (C) 2004 Lippincott Williams Wilkins.