To shed more light on the hepatocyte-specific role of Tgf-β signaling during liver fibrosis, we generated transgenic mice expressing constitutively active Tgf-β type I receptor Alk5 under the control of albumin promoter.
Therefore, the aim of our study was to investigate whether genetic variation in 3' untranslated region (3'UTR) of TGF-β receptor type I (TGFBR1) gene is associated with recurrence and severity of hepatitis C and liver fibrosis following OLT in HCV-infected patients.
These data suggest that HCV NS3 protease mimics TGF-β2 and functions, at least in part, via directly binding to and activating TβRI, thereby enhancing liver fibrosis.
This ALK5 inhibitor was then tested in a model of liver hepatectomy in TGF-beta-overexpressing transgenic mice, in an acute model of liver disease and in a chronic model of dimethylnitrosamine (DMN)-induced liver fibrosis.