Hepatocyte growth factor acts as a mitogen for equine satellite cells via protein kinase C δ-directed signaling
| Autor: | Amanda M Brandt, Joanna M Kania, Sally E. Johnson, Madison L Gonzalez |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Myoblast proliferation Protein Kinase C-alpha medicine.medical_treatment Myoblasts 03 medical and health sciences Genetics medicine Animals Humans Horses Phosphorylation RNA Small Interfering Protein kinase C Mitogen-Activated Protein Kinase 3 biology Myogenesis Chemistry Kinase Hepatocyte Growth Factor Growth factor Cell Differentiation General Medicine Cell cycle Molecular biology Protein Kinase C-delta 030104 developmental biology Mitogen-activated protein kinase biology.protein Animal Science and Zoology Hepatocyte growth factor Mitogens Cell Division Cell and Molecular Biology Food Science medicine.drug Signal Transduction |
| Zdroj: | Journal of animal science. 96(9) |
| ISSN: | 1525-3163 |
| Popis: | Hepatocyte growth factor (HGF) signals mediate mouse skeletal muscle stem cell, or satellite cell (SC), reentry into the cell cycle and myoblast proliferation. Because the athletic horse experiences exercise-induced muscle damage, the objective of the experiment was to determine the effect of HGF on equine SC (eqSC) bioactivity. Fresh isolates of adult eqSC were incubated with increasing concentrations of HGF and the initial time to DNA synthesis was measured. Media supplementation with HGF did not shorten (P > 0.05) the duration of G(0)/G(1) transition suggesting the growth factor does not affect activation. Treatment with 25 ng/mL HGF increased (P < 0.05) eqSC proliferation that was coincident with phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and AKT serine/threonine kinase 1 (AKT1). Chemical inhibition of the upstream effectors of ERK1/2 or AKT1 elicited no effect (P > 0.05) on HGF-mediated 5-ethynyl-2′-deoxyuridine (EdU) incorporation. By contrast, treatment of eqSC with 2 µm Gö6983, a pan-protein kinase C (PKC) inhibitor, blocked (P < 0.05) HGF-initiated mitotic activity. Gene-expression analysis revealed that eqSC express PKCα, PKCδ, and PKCε isoforms. Knockdown of PKCδ with a small interfering RNA (siRNA) prevented (P > 0.05) HGF-mediated EdU incorporation. The siPKCδ was specific to the kinase and did not affect (P > 0.05) expression of either PKCα or PKCε. Treatment of confluent eqSC with 25 ng/mL HGF suppressed (P < 0.05) nuclear myogenin expression during the early stages of differentiation. These results demonstrate that HGF may not affect activation but can act as a mitogen and modest suppressor of differentiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|