Interleukin-6 promotes myogenic differentiation of mouse skeletal muscle cells: role of the STAT3 pathway.

  title={Interleukin-6 promotes myogenic differentiation of mouse skeletal muscle cells: role of the STAT3 pathway.},
  author={Miriam Hoene and Heike Runge and H. U. H{\"a}ring and Erwin D. Schleicher and Cora Weigert},
  journal={American journal of physiology. Cell physiology},
  volume={304 2},
Myogenic differentiation of skeletal muscle cells is characterized by a sequence of events that include activation of signal transducer and activator of transcription 3 (STAT3) and enhanced expression of its target gene Socs3. Autocrine effects of IL-6 may contribute to the activation of the STAT3-Socs3 cascade and thus to myogenic differentiation. The importance of IL-6 and STAT3 for the differentiation process was studied in C2C12 cells and in primary mouse wild-type and IL-6(-/-) skeletal… 

Figures from this paper

Interleukin-6 Induces Myogenic Differentiation via JAK2-STAT3 Signaling in Mouse C2C12 Myoblast Cell Line and Primary Human Myoblasts

It is demonstrated that IL-6 has concentration- and time-dependent effects on both C2C12 mouse myoblast cell line and primary human myoblasts, and these effects are mediated by specific components of the JAK/STAT/SOCS pathway.

Acute myotube protein synthesis regulation by IL-6-related cytokines.

Results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes, however, IL- 6- or Lif-induced SOCS3 negatively regulates the activation of myotube protein synthesis.

Type I collagen promotes the migration and myogenic differentiation of C2C12 myoblasts via the release of interleukin-6 mediated by FAK/NF-κB p65 activation.

The effect of collagen I, a major ECM component in muscle tissue and a popular food supplement, on mouse C2C12 myoblast proliferation, migration and differentiation as well as the underlying mechanisms are reported on.

Mesenchymal Stem Cells Promote IL-6 Secretion and Suppress the Gene Expression of Proinflammatory Cytokines in Contractile C2C12 Myotubes.

The present findings suggest that MSCs transplantation or injection of their extracellular vesicles improve the therapeutic effect of exercise against sarcopenia without exacerbating inflammation.

Mesenchymal Stem Cells Alter the Inflammatory Response of C2C12 Mouse Skeletal Muscle Cells.

This study evaluated the paracrine effect of mouse MSCs on the inflammatory response of lipopolysaccharide (LPS)-stimulated C2C12 mouse myoblasts and exerted remarkable anti-inflammatory effects on LPS-stimulated mouse macrophages.

Supplementation with IL-6 and Muscle Cell Culture Conditioned Media Enhances Myogenic Differentiation of Adipose Tissue-Derived Stem Cells through STAT3 Activation

The modified protocol improved differentiation efficiency and reduced the time required for differentiation of myocytes and might be helpful to save cost and time when preparing myocytes for cell therapies and drug discovery.

IL-6 Impairs Myogenic Differentiation by Downmodulation of p90RSK/eEF2 and mTOR/p70S6K Axes, without Affecting AKT Activity

The study revealed that IL-6 induces the activation of the Stat3 signaling and promotes the downmodulation of the p90RSK/eEF2 and mTOR/p70S6K axes, while it does not affect theactivation of AKT, and identified potential molecular mediators of the inhibitory effects of IL- 6 on myogenic program.

Tumor Necrosis Factor Alpha and Insulin-Like Growth Factor 1 Induced Modifications of the Gene Expression Kinetics of Differentiating Skeletal Muscle Cells

This is the largest dataset revealing the impact of TNF-α or IGF1 treatment on gene expression kinetics of early in vitro skeletal myoblast differentiation and this is the first description of a specific inverse regulation of the following genes in myoblow differentiation and response to T NF-α.

IL-12 involvement in myogenic differentiation of C2C12 in vitro.

A novel role is identified for the cytokine IL-12, known to be a cytokine involved in inflammatory responses, which appears to be involved in the myogenic differentiation process, acting as a positive regulator of this mechanism.

Regulation of human satellite cells in vitro via inflammatory cytokines and myogenic transcription factors across proliferation and differentiation

This study used satellite cells cultured from the vastus lateralis of 12 male human research subjects, and ELISA analysis to measure levels of TNF-α and IL-6 across proliferation, early differentiation, and late differentiation and showed an 83% decrease in IL- 6 protein secretion 24 hours after exposure to differentiation media.

JAK/STAT signaling and human in vitro myogenesis

Insight is provided into JAK/STAT signaling in human skeletal muscle development, and recent observations in rodents are confirmed.

JAK1–STAT1–STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts

It is demonstrated that Janus kinase 1 (JAK1) is required for myoblast proliferation and that it also functions as a checkpoint to prevent myoblasts from premature differentiation.

JAK2/STAT2/STAT3 Are Required for Myogenic Differentiation*

A novel role for the JAK2/STAT2/ STAT3 pathway in myogenic differentiation is revealed, suggesting that this pathway could also promote differentiation by regulating signaling molecules known to be involved inMyogenic differentiation.

SOCS-3 Induces Myoblast Differentiation*

Overexpression of SOCS-3 cDNA significantly increased transcriptional activation of the 2.0-kb skeletal α-actin promoter in differentiating C2C12 myoblasts, indicating that SOCs-3 can contribute to the myoblast differentiation process in the absence of IGF-I.

Reciprocal Inhibition between MyoD and STAT3 in the Regulation of Growth and Differentiation of Myoblasts*

The results suggest that the development of muscle cells is regulated by the coordination of cytokine signals and intrinsic transcription factors.

Inhibition of Myoblast Differentiation by Tumor Necrosis Factor α Is Mediated by c-Jun N-terminal Kinase 1 and Leukemia Inhibitory Factor*

Studies with cell lines expressing MyoD:ER chimera and lacking JNK1 or JNK2 genes indicate that JNK 1 activity mediates the effects of TNFα on myoblast proliferation and differentiation, and TNF α promotes myOBlast proliferation through J NK1 and prevents my oblast differentiation through JNK3-mediated secretion of LIF.

Cardiotrophin-1 Maintains the Undifferentiated State in Skeletal Myoblasts*

Exogenous systemic expression of CT-1 mediated by adenoviral vector delivery increased the number of myonuclei in normal post-natal mouse skeletal muscle and also delayed skeletal muscle regeneration induced by cardiotoxin injection.

p38 MAPK-induced nuclear factor-kappaB activity is required for skeletal muscle differentiation: role of interleukin-6.

This study provides the first evidence of a crosstalk between p38 MAPK and NF-kappaB signaling pathways during myogenesis, with IL-6 being one of the effectors of this promyogenic mechanism.