Hepatocyte growth factor/scatter factor (HGF/SF) signals via the STAT3/APRF transcription factor in human hepatoma cells and hepatocytes.
Acute phase protein expression is regulated by a variety of cytokines such as IL-1, IL-6, IL-11, tumour necrosis factor alpha, interferon-gamma, oncostatin-M, leukemia inhibitory factor, ciliary neurotrophic factor and cardiotrophin-1. Presently, IL-6 is regarded as the most potent mediator of acute phase protein (APP) synthesis. It was shown that IL-6 and IL-6-type cytokines activate the so-called JAK/STAT pathway and finally regulate APP expression in liver cells. Since HGF/SF is also capable of regulating APP expression, we asked whether it might also signal via the JAK/STAT pathway. Here we show that incubation of human hepatocytes as well as hepatoma cells (HepG2) with HGF/SF results in activation of the transcription factor STAT3. This STAT3 activation after HGF/SF did not occur before 5-7 h and was maintained up to 28 h. These observations are in contrast to the rapid and transient activation of STAT1 and STAT3 mediated by IL-6.
Schaper
F
F
Institut für Biochemie der RWTH Aachen, Germany.
Siewert
E
E
Gómez-Lechon
M J
MJ
Gatsios
P
P
Sachs
M
M
Birchmeier
W
W
Heinrich
P C
PC
Castell
J
J
D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000514:alpha 1-Antichymotrypsin / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000514:alpha 1-Antichymotrypsin; D017228:Hepatocyte Growth Factor