The DOI matches its Crossref record; 54 of the 57 references it cites were found in a registry or an index.
Interleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy
Open accessAbstract
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.
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In the citing paper
“For instance, the pro-inflammatory cytokine IL-6 mediates lipid oxidation [7], induces the production of anti-inflammatory interleukins during exercise (e.g. IL-10 and IL-1ra) [8] and stimulates muscle growth [9].”
In the citing paper
“In vitro, IL-6 bears anabolic effects by regulating satellite cells’ function and enhancing glucose metabolism; furthermore, a loss of IL-6 signaling in myoblasts results in a reduced proliferation and migration [49,50].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [50]
In the citing paper
“Elimination of these cytokines in vivo has been shown to diminish muscle repair [118].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [118]
In the citing paper
“Briefly, a number of studies have shown that the chemokines and cytokines (TNF-α, IL-1β, IL-6) produced by initially infiltrating M1 macrophages are chemoattractant and mitogenic for muscle progenitor cells, including Pax7+ satellite cells [115–119].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [118]
In the citing paper
“Although the myokine IL-6 is mostly recognized for its regulatory effects in lipid and glucose metabolism, IL-6 also plays important roles in myogenesis.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [49]
In the citing paper
“Genetic loss of IL-6 impaired muscle hypertrophy in vivo, whereas myotube-produced IL-6 stimulated muscle cell proliferation in a paracrine fashion (49).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [49]
In the citing paper
“Although being considered pro-inflammatory, TNF-α and IL-6 also appear to play important role in the early stages of muscle regeneration following injury by enhancing myoblast proliferation and inhibiting differentiation [73,74,75].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [73]
In the citing paper
“This inhibition involves the down regulation of the MRFs, MyoD and Myogenin [73,74,75], with TNF-α receptor double knock out mice [74] and with IL-6 non-specific knock out mice [73] shown to present impaired myogenic differentiation and hypertrophy when compared to wild type mice during functional overloading.”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [73]
Citations
Cites
1 retracted
Immunohistochemical detection of interleukin‐6 in human skeletal muscle fibers following exercise
Penkowa, M., Keller, C., Keller, P., Jauffred, S., & Pedersen, B. K. (2003) · The FASEB Journal · doi:10.1096/fj.03-0311fje · Cited by 157
RetractedBodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768 · cited 1×
“…3 C57BL/6 background (WT) and generated by heterozygous mating of mice carrying a targeted disruption in which the second exon in the IL-6 gene was replaced by a neo r cassette (Kopf et al., 1994), were generously provided by A. Bernad (Centro Nacional de Investiga-ciones Cardiovasculares, Madrid).”
MethodNF-κB Controls Cell Growth and Differentiation through Transcriptional Regulation of Cyclin D1
D, D. C. G., Albanese, C., Reuther, J. Y., Pestell, R. G., & Baldwin, A. S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.8.5785 · Cited by 1,304
Correlation of Terminal Cell Cycle Arrest of Skeletal Muscle with Induction of p21 by MyoD
Halevy, O., Novitch, B. G., Spicer, D. B., Skapek, S. X., Rhee, J., Hannon, G. J., Beach, D., & Lassar, A. B. (1995) · Science · doi:10.1126/science.7863327 · Cited by 1,139
Skeletal muscle hypertrophy and atrophy signaling pathways
Glass, D. J. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.04.018 · Cited by 1,106
INTERLEUKIN-6: From Basic Science to Medicine—40 Years in Immunology
Kishimoto, T. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115806 · Cited by 1,040
Signalling pathways that mediate skeletal muscle hypertrophy and atrophy
Glass, D. J. (2003) · Nature Cell Biology · doi:10.1038/ncb0203-87 · Cited by 694
IL-6 signal transduction and its physiological roles: the signal orchestration model
Kamimura, D., Ishihara, K., & Hirano, T. (2003) · Reviews of Physiology, Biochemistry and Pharmacology · doi:10.1007/s10254-003-0012-2 · Cited by 673
IL-6-induced skeletal muscle atrophy
Haddad, F., Zaldivar, F., Cooper, D. M., & Adams, G. R. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01026.2004 · Cited by 612
Cited by
Sorted by citations
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909
Satellite Cells and the Muscle Stem Cell Niche
Yin, H., Price, F., & Rudnicki, M. A. (2013) · Physiological Reviews · doi:10.1152/physrev.00043.2011 · Cited by 2,166
“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).”
BackgroundResultMuscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis
Joe, A. W. B., Yi, L., Natarajan, A., Le Grand, F., So, L., Wang, J., Rudnicki, M. A., & Rossi, F. M. V. (2010) · Nature Cell Biology · doi:10.1038/ncb2015 · Cited by 1,690
Mechanisms regulating skeletal muscle growth and atrophy
Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492
Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226
“Genetic loss of IL-6 impaired muscle hypertrophy in vivo, whereas myotube-produced IL-6 stimulated muscle cell proliferation in a paracrine fashion (49).”
Background
Metadata
- Authors
- Serrano, A. L., Baeza-Raja, B., Perdiguero, E., Jardí, M., & Muñoz-Cánoves, P.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 7
- Issue
- 1
- Pages
- 33-44
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1997149085
- Cited by
- 873
- References
- 57
- Citations by year
- 2026: 43 · 2025: 56 · 2024: 42 · 2023: 55 · 2022: 71 · 2021: 73 · 2020: 48 · 2019: 55 · 2018: 50 · 2017: 54 · 2016: 45 · 2015: 69 · 2014: 42 · 2013: 48 · 2012: 51
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2024 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association Française contre les Myopathies (Marató-TV3)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Muscular Dystrophy Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- interleukin-6, satellite cells, skeletal muscle hypertrophy, muscle stem cells, STAT3 signaling, cyclin D1, myonuclear accretion, satellite cell proliferation, paracrine signaling, myofiber growth, cytokine deficiency
- MeSH terms
- Animals, Cell Line, Cell Movement, Enzyme-Linked Immunosorbent Assay, Hypertrophy, Immunohistochemistry, Muscular Diseases, Blotting, Western, Interleukin-6, Mice, Knockout, Muscle, Skeletal, Muscle Fibers, Skeletal, Cyclin D1, Reverse Transcriptase Polymerase Chain Reaction, Myoblasts, Satellite Cells, Skeletal Muscle, Cell Proliferation, STAT3 Transcription Factor, Mice
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