Hepatocyte growth factor acts as a mitogen for equine satellite cells via protein kinase C δ-directed signaling.
Abstract: 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 G0/G1 transition suggesting the growth factor does not affect activation. Treatment with 25 ng/mL HGF increased (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-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.
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Publication Date: 2018-06-20 PubMed ID: 29917108PubMed Central: PMC6127786DOI: 10.1093/jas/sky234Google Scholar: Lookup
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Summary
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This research article explores how Hepatocyte growth factor (HGF) affects the bioactivity of equine satellite cells (eqSC). The findings reveal that HGF does not impact cell activation but can act as a growth stimulant and a slight suppressor of cell differentiation.
Research Overview
- The study aimed to examine how Hepatocyte growth factor (HGF) influences the bioactivity of equine satellite cells (eqSC), which are vital for muscle repair and regeneration in horses.
- The researchers conducted experiments on fresh eqSC isolates, which were treated with varying concentrations of HGF, and then the initial time to DNA synthesis was measured.
Key Findings
- The study discovered that HGF does not shorten the duration of the G0/G1 transition, indicating that this growth factor has no impact on cell activation.
- However, upon treatment with 25 ng/mL of HGF, eqSC proliferation was observed along with the phosphorylation of ERK1/2 and AKT1, proteins that play significant roles in cell division and survival.
- Surprisingly, the inhibition of upstream activators of ERK1/2 or AKT1 had no effect on HGF-mediated EdU incorporation, a measure of cell proliferation.
- On the other hand, the use of a protein kinase C (PKC) inhibitor effectively blocked HGF-induced mitotic activity, indicating an essential role of PKC in the HGF-directed signaling pathway for eqSC proliferation.
Further Insights
- Gene expression analysis revealed that eqSC express PKCα, PKCδ, and PKCε isoforms.
- A targeted knockdown of PKCδ with a small interfering RNA (siRNA) effectively prevented HGF-mediated EdU incorporation, further underlining the role of PKC in this process.
- The siRNA used was specific to PKCδ and had no observable impact on the expression of other PKC isoforms, namely PKCα and PKCε.
- Finally, it was observed that treatment of eqSC with 25 ng/mL HGF suppressed nuclear myogenin expression during early differentiation stages showing that HGF has a modest inhibitory effect on differentiation processes.
Cite This Article
APA
Brandt AM, Kania JM, Gonzalez ML, Johnson SE.
(2018).
Hepatocyte growth factor acts as a mitogen for equine satellite cells via protein kinase C δ-directed signaling.
J Anim Sci, 96(9), 3645-3656.
https://doi.org/10.1093/jas/sky234 Publication
Researcher Affiliations
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg VA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg VA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg VA.
- Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg VA.
MeSH Terms
- Animals
- Cell Differentiation / physiology
- Cell Division
- Hepatocyte Growth Factor / physiology
- Horses / genetics
- Horses / metabolism
- Humans
- Mitogen-Activated Protein Kinase 3
- Mitogens
- Myoblasts
- Phosphorylation
- Protein Kinase C-alpha
- Protein Kinase C-delta / physiology
- RNA, Small Interfering / metabolism
- Signal Transduction
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Citations
This article has been cited 5 times.- Johnson SE, Barshick MR, Gonzalez ML, Riley JW, Pelletier ME, Castanho BC, Ealy EN. A Carnitine-Containing Product Improves Aspects of Post-Exercise Recovery in Adult Horses.. Animals (Basel) 2023 Feb 14;13(4).
- Barshick MR, Gonzalez ML, Busse NI, Helsel PJ, Johnson SE. The initial delay to mitotic activity in primary cultures of equine satellite cells is reduced by combinations of growth factors.. J Anim Sci 2022 Aug 1;100(8).
- Busse NI, Gonzalez ML, Wagner AL, Johnson SE. Short Communication: Supplementation with calcium butyrate causes an increase in the percentage of oxidative fibers in equine gluteus medius muscle.. J Anim Sci 2022 Aug 1;100(8).
- Gonzalez ML, Busse NI, Waits CM, Johnson SE. Satellite cells and their regulation in livestock.. J Anim Sci 2020 May 1;98(5).
- Gonzalez ML, Jacobs RD, Ely KM, Johnson SE. Dietary tributyrin supplementation and submaximal exercise promote activation of equine satellite cells.. J Anim Sci 2019 Dec 17;97(12):4951-4956.
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