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-ga mma, oncostatin-M, leukemia inhibitory factor, ciliary neurotrophic fa ctor and cardiotrophin-1. Presently, IL-6 is regarded as the most pote nt mediator of acute phase protein (APP) synthesis, It was shown that IL-6 and IL-6-type cytokines activate the so-called JAR/STAT pathway a nd finally regulate APP expression in liver cells, Since HGF/SF is als o capable of regulating APP expression, me asked whether it might also signal via the JAK/STAT pathway, Here we show that incubation of huma n hepatocytes as well as hepatoma cells (HepG2) with HGF/SF results in activation of the transcription factor STAT3. This STAT3 activation a fter 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 activati on of STAT1 and STAT3 mediated by IL-6. (C) 1997 Federation of Europea n Biochemical Societies.