Roles of TGF-beta in hepatic fibrosis.
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 action 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 cross-talk 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 strategies aim at inhibition of TGF-beta1 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.
Gressner
Axel M
AM
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, D-52074 Aachen, Germany. agressner@ukaachen.de
Weiskirchen
Ralf
R
Breitkopf
Katja
K
Dooley
Steven
S
D028341:Activins / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D008954:Models, Biological; D008958:Models, Molecular; D051381:Rats; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D028341:Activins