Loss of TGF-{beta} dependent growth control during HSC transdifferentiation

Journal Article · Fri Feb 16 04:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.12.125· OSTI ID:20979802

Purps, Oliver ^[1]; Lahme, Birgit ^[1]; Gressner, Axel M ^[1]; Meindl-Beinker, Nadja M ^[2]; Dooley, Steven ^[2]

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1. Institute of Clinical Chemistry and Pathobiochemistry, University Hospital, RWTH-Aachen (Germany)
2. 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, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 353; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BILIARY TRACT
BIOSYNTHESIS
CELL PROLIFERATION
DNA
INHIBITION
LIVER
LIVER CELLS
LYMPHOKINES
RATS
RECEPTORS
RETICULOENDOTHELIAL SYSTEM