Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways. (June 2015)

• Record Type: Journal Article
• Authors: Walker, Nicholas; Kahamba, Trish; Woudberg, Nicholas; Goetsch, Kyle; Niesler, Carola
• Is Part Of: Growth factors. Volume 33:Number 3(2015:Jun.)
• Page Start: 229
• Page End: 241
• Publication Date: 2015-06
• Subjects: Growth factors -- Periodicals; Physiology -- Periodicals; 611
• Languages: English
• ISSNs: 0897-7194

Abstract

<abstract> <title>Abstract</title> <p>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 <italic>decreased</italic> expression in differentiating cells cultured with 2 ng/ml HGF, but <italic>increased</italic> 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.</p> </abstract>