EPO-receptor is present in mouse C2C12 and human primary skeletal muscle cells but EPO does not influence myogenesis

Séverine Lamon, Evelyn Zacharewicz, Andrew N. Stephens, Aaron P. Russell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The role and regulation of the pleiotropic cytokine erythropoietin (EPO) in skeletal muscle are controversial. EPO exerts its effects by binding its specific receptor (EPO-R), which activates intracellular signaling and gene transcription in response to internal and external stress signals. EPO is suggested to play a direct role in myogenesis via the EPO-R, but several studies have questioned the effect of EPO treatment in muscle in vitro and in vivo. The lack of certainty surrounding the use of nonspecific EPO-R antibodies contributes to the ambiguity of the field. Our study demonstrates that the EPO-R gene and protein are expressed at each stage of mouse C2C12 and human skeletal muscle cell proliferation and differentiation and validates a specific antibody for the detection of the EPO-R protein. However, in our experimental conditions, EPO treatment had no effect on mouse C2C12 and human muscle cell proliferation, differentiation, protein synthesis or EPO-R expression. While an increase in Akt and MAPK phosphorylation was observed, we demonstrate that this effect resulted from the stress caused by changing medium and not from EPO treatment. We therefore suggest that skeletal muscle EPO-R might be present in a nonfunctional form, or too lowly expressed to play a role in muscle cell function.

Original languageEnglish
Article numbere00256
JournalPhysiological Reports
Volume2
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Cytokine
  • Erythropoietin
  • Erythropoietinreceptor
  • Myogenesis
  • Skeletal muscle

Cite this

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title = "EPO-receptor is present in mouse C2C12 and human primary skeletal muscle cells but EPO does not influence myogenesis",
abstract = "The role and regulation of the pleiotropic cytokine erythropoietin (EPO) in skeletal muscle are controversial. EPO exerts its effects by binding its specific receptor (EPO-R), which activates intracellular signaling and gene transcription in response to internal and external stress signals. EPO is suggested to play a direct role in myogenesis via the EPO-R, but several studies have questioned the effect of EPO treatment in muscle in vitro and in vivo. The lack of certainty surrounding the use of nonspecific EPO-R antibodies contributes to the ambiguity of the field. Our study demonstrates that the EPO-R gene and protein are expressed at each stage of mouse C2C12 and human skeletal muscle cell proliferation and differentiation and validates a specific antibody for the detection of the EPO-R protein. However, in our experimental conditions, EPO treatment had no effect on mouse C2C12 and human muscle cell proliferation, differentiation, protein synthesis or EPO-R expression. While an increase in Akt and MAPK phosphorylation was observed, we demonstrate that this effect resulted from the stress caused by changing medium and not from EPO treatment. We therefore suggest that skeletal muscle EPO-R might be present in a nonfunctional form, or too lowly expressed to play a role in muscle cell function.",
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EPO-receptor is present in mouse C2C12 and human primary skeletal muscle cells but EPO does not influence myogenesis. / Lamon, Séverine; Zacharewicz, Evelyn; Stephens, Andrew N.; Russell, Aaron P.

In: Physiological Reports, Vol. 2, No. 3, e00256, 2014.

Research output: Contribution to journalArticleResearchpeer-review

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