Double-knockout (DKO) mice exhibit activation of transforming growth factor (TGF)-β pathway in the liver. A: Heat maps exhibiting differential expression of several selective TGF-β pathway-related genes in the DKO livers compared with control (CON). B: Real-time quantitative PCR analysis showing relative mRNA expression of several components of the TGF-β pathway signaling in the DKO versus CON livers. C: Immunohistochemistry showing phosphorylated SMAD2 in hepatocytes in DKO and not CON livers. D: TGF-β pathway target matrix metalloproteinase (MMP) 9 in hepatocytes in the DKO livers compared with CON. E: Western blot analysis showing hepatocyte nuclear factor 4α (HNF4α) expression in Hep3B cells on siRNA-mediated knockdown of β-catenin and γ-catenin, in the presence of varying doses of TGF-β inhibitor. ∗P < 0.05 versus WT. Scale bars = 10 μm (C and D). GAPDH, glyceraldehyde-3-phosphate dehydrogenase; G6PC, glucose-6-phosphatase, catalytic subunit; TIMP, tissue inhibitor of metalloproteinases; WT, wild type.