Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways

作者：Walker Nicholas; Kahamba Trish; Woudberg Nicholas; Goetsch Kyle; Niesler Carola^*

来源：Growth Factors, 2015, 33(3): 229-241.

DOI：10.3109/08977194.2015.1058260

• c-Met
• hepatocyte growth factor
• MAPK
• myogenesis
• myoblast
• PI3K

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 10ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2ng/ml HGF, but increased expression in proliferating cells with 10ng/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.

• 出版日期2015-5-4