TGF-β/Smad-signaling in liver cells: Target genes and inhibitors of two parallel pathways

Transforming growth factor (TGF)-β is a major mediator of fibrosis in diverse organs/tissues, including liver, due to its gene regulatory properties that lead to high expression and secretion of extracellular matrix components. Whereas the canonical Smad pathway seems to be very simple, TGF-β turns out to be a multiplicity factor with a highly cell type specific outcome and therefore, no universally valid plan of its signal transduction can be formulated. In the present review, we will summarize information about the Smad dependent and Smad independent TGF-β signaling network in hepatic stellate cells (HSCs) and hepatocytes, with emphasis on its role in chronic liver disease. In addition, current state of the art anti-TGF-β strategies for liver fibrosis treatment are discussed.