Cirrhotic hepatocytes exhibit decreased TGFβ growth inhibition associated with downregulated Smad protein expression

TGFβ controls hepatocyte growth through cell cycle arrest and apoptosis, and resistance to TGFβ is a mechanism of malignant transformation. The aim of this study was to assess differences in TGFβ-mediated growth inhibition in normal and cirrhotic hepatocytes. Cirrhosis was induced in mice and normal and cirrhotic hepatocytes were isolated by collagenase perfusion and treated with or without TGFβ (5 ng/ml). DNA synthesis, Smad protein expression, and DNA binding activity were determined. TGFβ reduced DNA synthesis to a greater degree in normal hepatocytes than in cirrhotic hepatocytes (87% vs. 68%; p