Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways
| Autor: | Nicholas Walker, K.P. Goetsch, Trish Kahamba, Nicholas J. Woudberg, Carola U. Niesler |
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| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
C-Met Satellite Cells Skeletal Muscle MAP Kinase Signaling System medicine.medical_treatment Clinical Biochemistry Muscle Development p38 Mitogen-Activated Protein Kinases Cell Line chemistry.chemical_compound Mice Endocrinology medicine Animals Humans Extracellular Signal-Regulated MAP Kinases PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Myogenesis Hepatocyte Growth Factor Growth factor JNK Mitogen-Activated Protein Kinases Cell Differentiation Cell Biology Proto-Oncogene Proteins c-met Cell biology chemistry Hepatocyte growth factor Cell activation C2C12 Cell Division medicine.drug |
| Zdroj: | Growth factors (Chur, Switzerland). 33(3) |
| ISSN: | 1029-2292 |
| Popis: | Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2 ng/ml HGF, but increased expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF-mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling. |
| Databáze: | OpenAIRE |
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