Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy.

By A. Serrano, B. Baeza-Raja, Eusebio Perdiguero, M. Jardí, P. Muñoz-Cánoves. Cell Metabolism, 2008

849 citations recorded by the source corpus.

Skeletal muscles adapt to increasing workload by augmenting their fiber size, through mechanisms that are poorly understood. This study identifies the cytokine interleukin-6 (IL-6) as an essential regulator of satellite cell (muscle stem cell)-mediated hypertrophic muscle growth. IL-6 is locally and transiently produced by growing myofibers and associated satellite cells, and genetic loss of IL-6 blunted muscle hypertrophy in vivo. IL-6 deficiency abrogated satellite cell proliferation and myonuclear accretion in the preexisting myofiber by impairing STAT3 activation and expression of its target gene cyclin D1. The growth defect was indeed muscle cell intrinsic, since IL-6 loss also affected satellite cell behavior in vitro, in a STAT3-dependent manner. Myotube-produced IL-6 further stimulated cell proliferation in a paracrine fashion. These findings unveil a role for IL-6 in hypertrophic muscle growth and provide mechanistic evidence for the contribution of satellite cells to this process.

Subfields: Genetics, Molecular Biology, Rehabilitation

View Paper: https://www.semanticscholar.org/paper/ed90b8032c69b0215ef259830817748fc604a136

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Citations in the corpus

Leucocytes, cytokines and satellite cells: what role do they play in muscle damage and regeneration following eccentric exercise? (2012, background): “In contrast with TNF-α and MCP-1, IL-6 deficiency does not appear to alter muscle regeneration, even though IL-6 expression in muscle increases following injury (313) and IL-6 regulates the proliferation and differentiation of myoblasts (17,267).”
Macrophage polarization: An opportunity for improved outcomes in biomaterials and regenerative medicine (2012, background): “Elimination of these cytokines in vivo has been shown to diminish muscle repair [118].”
Exercise is the real polypill. (2013, background): “Other potential roles of IL-6 are stimulation of muscle growth (7, 441) and angiogenesis (172).”
Regulatory interactions between muscle and the immune system during muscle regeneration. (2010, background): “Although IL-6 ablation had no effect on the number of MyoD cells, at 3 days of muscle overloading in vivo, the number of myogenin cells at that time point decreased significantly (99), suggesting that the transition from the proliferative stage to the early differentiation stage of myogenesis was im”
Satellite Cells and Skeletal Muscle Regeneration (2015, neutral): “At physiological concentration, these cytokines are known to stimulate satellite cell activation and proliferation (58, 91, 272).”
Satellite cells and the muscle stem cell niche. (2013, background): “Furthermore, it was shown that the proliferation of satellite cells from IL-6 / mice was impaired both in vivo and in vitro, which is due to the attenuation of STAT3 signaling (480).”
Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020, background): “Genetic loss of IL-6 impaired muscle hypertrophy in vivo, whereas myotube-produced IL-6 stimulated muscle cell proliferation in a paracrine fashion (49).”