Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway
| Autor: | Goshi Shiota, Akihiro Kurimasa, Kazuya Matsumoto, Sakiko Yasui, Yoshikazu Murawaki, Jun-ichi Okano, Pablo Steinberg, Ichiro Hisatome |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
C-Met
Biophysics P70-S6 Kinase 1 Protein Serine-Threonine Kinases Biology Biochemistry Phosphatidylinositol 3-Kinases chemistry.chemical_compound Multienzyme Complexes Proto-Oncogene Proteins medicine LY294002 Molecular Biology Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Hepatocyte Growth Factor Akt/PKB signaling pathway Stem Cells Cell Biology Proto-Oncogene Proteins c-met Transforming Growth Factor alpha Liver Regeneration Cell biology Thrombopoietin chemistry Hepatocytes Cancer research Institut für Ernährungswissenschaft Hepatocyte growth factor Signal transduction Proto-Oncogene Proteins c-akt Cell Division Signal Transduction medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 309:298-304 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2003.04.002 |
| Popis: | Hepatocyte growth factor (HGF) is a potent mitogen for a variety of cells including hepatocytes. While rat oval cells are supposed to be one of hepatic stem cells, biological effects of HGF on oval cells and their relevant signal transduction pathways remain to be determined. We sought to investigate them on OC/CDE22 rat oval cells, which are established from the liver of rats fed a choline-deficient/DL-ethionine-supplemented diet. The oval cells were cultured on fibronectin-coated dishes and stimulated with recombinant HGF, transforming growth factor-α (TGF-α), and thrombopoietin (TPO) under the serum-free medium condition. HGF treatment enhanced [ 3 H]thymidine incorporation into oval cells in a dose-dependent manner. On the contrary, treatment with TGF-α or TPO had no significant effects on [ 3 H]thymidine incorporation into the oval cells. c-Met protein was phosphorylated at the tyrosine residues after the HGF treatment. AKT, extracellular signal-regulated kinase 1/2 (ERK1/2), and p70 s6k were simultaneously activated after the HGF stimulation, peaking at 30 min after the treatment. The activation of AKT, p70 s6k , and ERK1/2 induced by HGF was abolished by pre-treatment with LY294002, a phosphoinositide 3-OH kinase (PI3K) inhibitor, and U0126, a mitogen-activated protein kinase/ERK kinase (MEK) inhibitor, respectively. When the cells were pre-treated with LY294002 prior to the HGF stimulation, the proliferative action of HGF was completely abrogated, implying that the PI3K/AKT signaling pathway is responsible for the biological effect of HGF. These in vitro data indicate that HGF exerts a proliferative action on hepatic oval cells via activation of the PI3K/AKT signaling pathway. |
| Databáze: | OpenAIRE |
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