Interleukin-6 promotes myogenic differentiation of mouse skeletal muscle cells: role of the STAT3 pathway
Abstract
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 muscle cells. In differentiating C2C12 myoblasts, the upregulation of IL-6 mRNA expression and protein secretion started after increased phosphorylation of STAT3 on tyrosine 705 and increased mRNA expression of Socs3 was observed. Knockdown of STAT3 and IL-6 mRNA in differentiating C2C12 myoblasts impaired the expression of the myogenic markers myogenin and MyHC IIb and subsequently myotube fusion. However, the knockdown of IL-6 did not prevent the induction of STAT3 tyrosine phosphorylation. The IL-6-independent activation of STAT3 was verified in differentiating primary IL-6(-/-) myoblasts. The phosphorylation of STAT3 and the expression levels of STAT3, Socs3, and myogenin during differentiation were comparable in the primary myoblasts independent of the genotype. However, IL-6(-/-) cells failed to induce MyHC IIb expression to the same level as in wild-type cells and showed reduced myotube formation. Supplementation of IL-6 could partially restore the fusion of IL-6(-/-) cells. These…
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IL-6 regulates protein homeostasis in skeletal muscle.
“IL‐6 regulates protein homeostasis in the skeletal muscle.”
From Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting (2022) · cites this paper as [14]
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References 36 · Cited by 110
- Authors
- Hoene, M., Runge, H., Häring, H. U., Schleicher, E. D., & Weigert, C.
- Affiliations
- Helmholtz Munich (DE)
- University of Tübingen (DE)
- Corresponding author
- Weigert, Cora
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2013-01-15
- Volume
- 304
- Issue
- 2
- Pages
- C128-C136
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2112937668
- Cited by
- 110
- References
- 36
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 3 · 2023: 10 · 2022: 10 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 9 · 2015: 7 · 2014: 5 · 2013: 5
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- interleukin-6, myogenesis, STAT3, SOCS3, skeletal myoblasts, myotube fusion, myogenin, STAT3 tyrosine phosphorylation, autocrine signaling, C2C12 myoblasts
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, Cell Differentiation, Cells, Cultured, Mice, Mutant Strains, Phosphorylation, Tyrosine, Signal Transduction, Interleukin-6, Myogenin, Muscle Fibers, Skeletal, Myosin Heavy Chains, Muscle Development, Myoblasts, Skeletal, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice, Gene Knockdown Techniques
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