title: TGF-beta/Smad signaling in the injured liver.
abstract: TGF-beta, acting both directly and indirectly, represents a central mediator of fibrogenic remodeling processes in the liver. Besides hepatic stellate cells (HSCs), which are induced by TGF-beta to transdifferentiate to myofibroblasts and to produce extracellular matrix, hepatocytes are also strongly responsive for this cytokine, which induces apoptosis during fibrogenesis and provides growth control in regeneration processes. Based on this, TGF-beta-mediated hepatic responses to injury are the result of a complex interplay between the different liver cell types. In this review we summarize the knowledge about TGF-beta signal transduction in HSCs with special impact on Smad pathways. We further describe a molecular cross-talk between profibrogenic TGF-beta and antifibrogenic IFN-gamma signaling in liver cells. Finally, we introduce hepatocyte plasticity and epithelial-to-mesenchymal transition in the liver, which is well established in tumorigenesis, as a potential feature of fibrogenesis and highlight possible action points of TGF-beta in these contexts.
authors.affiliation: Department of Medicine II, Division of Molecular Alcohol Research in Gastroenterology, University Hospital of Heidelberg at Mannheim. katja.breitkopf@med.ma.uni-heidelberg.de
authors.forename: K
authors.initials: K
authors.lastname: Breitkopf
authors.forename: P
authors.initials: P
authors.lastname: Godoy
authors.forename: L
authors.initials: L
authors.lastname: Ciuclan
authors.forename: M V
authors.initials: MV
authors.lastname: Singer
authors.forename: S
authors.initials: S
authors.lastname: Dooley
mesh_terms: D000818:Animals; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta