Loss of TGF-{beta} dependent growth control during HSC transdifferentiation
- Institute of Clinical Chemistry and Pathobiochemistry, University Hospital, RWTH-Aachen (Germany)
- Center of Molecular Alcohol Research, II. Medical Clinic, Faculty of Medicine at Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany)
Liver injury induces activation of hepatic stellate cells (HSCs) comprising expression of receptors, proliferation, and extracellular matrix synthesis triggered by a network of cytokines provided by damaged hepatocytes, activated Kupffer cells and HSCs. While 6 days after bile duct ligation in rats TGF-{beta} inhibited DNA synthesis in HSCs, it was enhanced after 14 days, indicating a switch from suppression to DNA synthesis stimulation during fibrogenesis. To delineate mechanisms modulating TGF-{beta} function, we analyzed crosstalk with signaling pathways initiated by cytokines in damaged liver. Lipopolysaccharide and tumor necrosis factor-{alpha} enhanced proliferation inhibition of TGF-{beta}, whereas interleukin-6, oncostatin M, interleukin-1{alpha}, and interleukin-1{beta} did not. Hepatocyte growth factor (HGF) counteracted TGF-{beta} dependent inhibition of DNA synthesis in quiescent HSCs. Since expression of c-met is induced during activation of HSCs and HGF is overrepresented in damaged liver, crosstalk of HGF and TGF-{beta} contributes to loss of TGF-{beta} dependent inhibition of DNA synthesis in HSCs.
- OSTI ID:
- 20979802
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 353, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2006.12.125; PII: S0006-291X(06)02804-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-{kappa}B/TGF-{beta}{sub 1} pathway
Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells