title: Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways.
abstract: 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.
authors.affiliation: a Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal , Scottsville , South Africa.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Walker
authors.affiliation: a Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal , Scottsville , South Africa.
authors.forename: Trish
authors.initials: T
authors.lastname: Kahamba
authors.affiliation: a Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal , Scottsville , South Africa.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Woudberg
authors.affiliation: a Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal , Scottsville , South Africa.
authors.forename: Kyle
authors.initials: K
authors.lastname: Goetsch
authors.affiliation: a Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal , Scottsville , South Africa.
authors.forename: Carola
authors.initials: C
authors.lastname: Niesler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D024510:Muscle Development / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C066855:HGF protein, human; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: MAPK; PI3K; c-Met; hepatocyte growth factor; myoblast; myogenesis