Interleukin-6 Induces myogenic differentiation via JAK2-STAT3 signaling in mouse C2C12 myoblast cell line and primary human myoblasts
| dc.contributor.author | Steyn, Paul J. | en_ZA |
| dc.contributor.author | Dzobo, Kevin | en_ZA |
| dc.contributor.author | Smith, Robert I. | en_ZA |
| dc.contributor.author | Myburgh, Kathryn H. | en_ZA |
| dc.date.accessioned | 2019-10-31T10:03:31Z | |
| dc.date.available | 2019-10-31T10:03:31Z | |
| dc.date.issued | 2019-10-24 | |
| dc.description | CITATION: Steyn, P. J., et al. 2018. Interleukin-6 Induces myogenic differentiation via JAK2-STAT3 signaling in mouse C2C12 myoblast cell line and primary human myoblasts. International Journal of Molecular Sciences, 20(21):5273, doi:10.3390/ijms20215273. | en_ZA |
| dc.description | The original publication is available at http://www.mdpi.com | en_ZA |
| dc.description | Publication of this article was funded by the Stellenbosch University Open Access Fund. | en_ZA |
| dc.description.abstract | Postnatal muscle growth and exercise- or injury-induced regeneration are facilitated by myoblasts. Myoblasts respond to a variety of proteins such as cytokines that activate various signaling cascades. Cytokines belonging to the interleukin 6 superfamily (IL-6) influence myoblasts’ proliferation but their effect on differentiation is still being researched. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is one of the key signaling pathways identified to be activated by IL-6. The aim of this study was to investigate myoblast fate as well as activation of JAK-STAT pathway at different physiologically relevant IL-6 concentrations (10 pg/mL; 100 pg/mL; 10 ng/mL) in the C2C12 mouse myoblast cell line and primary human myoblasts, isolated from eight young healthy male volunteers. Myoblasts’ cell cycle progression, proliferation and differentiation in vitro were assessed. Low IL-6 concentrations facilitated cell cycle transition from the quiescence/Gap1 (G0/G1) to the synthesis (S-) phases. Low and medium IL-6 concentrations decreased the expression of myoblast determination protein 1 (MyoD) and myogenin and increased proliferating cell nuclear antigen (PCNA) expression. In contrast, high IL-6 concentration shifted a larger proportion of cells to the pro-differentiation G0/G1 phase of the cell cycle, substantiated by significant increases of both MyoD and myogenin expression and decreased PCNA expression. Low IL-6 concentration was responsible for prolonged JAK1 activation and increased suppressor of cytokine signaling 1 (SOCS1) protein expression. JAK-STAT inhibition abrogated IL-6-mediated C2C12 cell proliferation. In contrast, high IL-6 initially increased JAK1 activation but resulted in prolonged JAK2 activation and elevated SOCS3 protein expression. High IL-6 concentration decreased interleukin-6 receptor (IL-6R) expression 24 h after treatment whilst low IL-6 concentration increased IL-6 receptor (IL-6R) expression at the same time point. In conclusion, this study demonstrated that IL-6 has concentration- and time-dependent effects on both C2C12 mouse myoblasts and primary human myoblasts. Low IL-6 concentration induces proliferation whilst high IL-6 concentration induces differentiation. These effects are mediated by specific components of the JAK/STAT/SOCS pathway. | en_ZA |
| dc.description.uri | https://www.mdpi.com/1422-0067/20/21/5273 | |
| dc.description.version | Publisher's version | en_ZA |
| dc.format.extent | 30 pages : illustrations | en_ZA |
| dc.identifier.citation | Steyn, P. J., et al. 2018. Interleukin-6 Induces myogenic differentiation via JAK2-STAT3 signaling in mouse C2C12 myoblast cell line and primary human myoblasts. International Journal of Molecular Sciences, 20(21):5273, doi:10.3390/ijms20215273 | en_ZA |
| dc.identifier.issn | 1422-0067 (online) | |
| dc.identifier.issn | 1661-6596 (print) | |
| dc.identifier.other | doi:10.3390/ijms20215273 | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/106756 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | MDPI | en_ZA |
| dc.rights.holder | Authors retain copyright | en_ZA |
| dc.subject | Myogenesis | en_ZA |
| dc.subject | Myoblasts proliferation | en_ZA |
| dc.subject | Interleukin 6 | en_ZA |
| dc.subject | Muscles -- Regeneration | en_ZA |
| dc.subject | Myoblasts differentiation | en_ZA |
| dc.subject | Muscle satellite cells | en_ZA |
| dc.title | Interleukin-6 Induces myogenic differentiation via JAK2-STAT3 signaling in mouse C2C12 myoblast cell line and primary human myoblasts | en_ZA |
| dc.type | Article | en_ZA |