[Frontiers in Bioscience 7, d793-807, April 1, 2002]


Axel M. Gressner, Ralf Weiskirchen, Katja Breitkopf, Steven Dooley

Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, D-52074 Aachen, Germany


1. Abstract
2. Transforming Growth Factor-beta in the Liver: Structure, Processing and Function
3. TGF-beta Signal Transduction in Liver Cells
4. Hepatic Stellate Cell Activation
5. TGF-beta and activin induced parenchymal cell apoptosis
6. The Potential of Circulating TGF-β as a Diagnostic Tool
7. Therapeutic antagonism of TGF-beta
8. Outlook and future perspectives
9. References


TGF-beta has multiple profibrogenic but also anti-inflammatory and immunosuppressive effects. The balance of these actions is required for maintaining tissue homeostasis and an aberrant expression of TGF-beta is involved in a number of disease processes in the liver. In addition to its fibrogenic effects leading to transdifferentiation of hepatic stellate cells into myofibroblasts, TGF-beta is also an important negative regulator of proliferation and an inducer of apoptosis. The major portion of TGF-beta is secreted as part of an inactive complex and the details of the activation process in liver have not yet been elucidated. The initially striking simplicity of the core TGF-beta /Smad signaling pathways is rapidly giving way to a much more complex view of intracellular signal transduction mechanisms and recent work has demonstrated the importance of crosstalk among different signaling pathways to either specify, enhance, or inhibit TGF-beta responses. The ubiquitous pathophysiologic relevance of TGF-beta suggests its measurement in blood as a diagnostic tool. Other approaches aim at inhibition of TGF-beta 1 function or synthesis as a primary target for the development of antifibrotic strategies and recent advances in cell biology have opened several ways to approach the inhibition of TGF-beta action.