Hepatocyte growth factor/scatter factor (HGF/SF) signals via the STAT3/APRF transcription factor in human hepatoma cells and hepatocytes

FEBS Lett. 1997 Mar 17;405(1):99-103. doi: 10.1016/s0014-5793(97)00167-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • STAT3 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • alpha 1-Antichymotrypsin / biosynthesis

Substances

  • DNA-Binding Proteins
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Transcription Factors
  • alpha 1-Antichymotrypsin
  • Hepatocyte Growth Factor