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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]
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“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
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“Genetic loss of IL-6 impaired muscle hypertrophy in vivo, whereas myotube-produced IL-6 stimulated muscle cell proliferation in a paracrine fashion (49).”
BackgroundRegulatory interactions between muscle and the immune system during muscle regeneration
Tidball, J. G., & Villalta, S. A. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00735.2009 · Cited by 1,105
“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 impaired by the loss…”
BackgroundBrown, B. N., Ratner, B. D., Goodman, S. B., Amar, S., & Badylak, S. F. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.02.034 · Cited by 926
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Heredia, J. E., Mukundan, L., Chen, F. M., Mueller, A. A., Deo, R. C., Locksley, R. M., Rando, T. A., & Chawla, A. (2013) · Cell · doi:10.1016/j.cell.2013.02.053 · Cited by 818
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“Other potential roles of IL-6 are stimulation of muscle growth (7, 441) and angiogenesis (172).”
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Self-citationMuscle damage and inflammation during recovery from exercise.
Peake, J., Neubauer, O., Gatta, P. D. D., & Nosaka, K. (2016) · Journal of applied physiology · doi:10.1152/japplphysiol.00971.2016 · Cited by 740
Macrophages in inflammation, repair and regeneration
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Satellite Cells and Skeletal Muscle Regeneration
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A review on the mechanisms of blood-flow restriction resistance training-induced muscle hypertrophy
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“Exercise-induced muscle damage (EIMD) is purported to be an essential regulator of satellite cell-mediated compensatory muscle growth (see later section) [52–54].”
BackgroundSarcopenia and type 2 diabetes mellitus: a bidirectional relationship
Mesinovic, J., Zengin, A., de Courten, B. V., Ebeling, P. R., & Scott, D. S. (2019) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s186600 · Cited by 603
“43 Contrary to this, IL-6 has been reported to cause muscle atrophy when localized to the tibialis anterior of Sprague-Dawley rats, independent of systemic in fl ammation.”
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Growth and the regulation of myotomal muscle mass in teleost fish
Johnston, I. A., Bower, N. I., & Macqueen, D. J. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.038620 · Cited by 494
“IL-6 has been shown to have a role in myogenic precursor cell-mediated fibre hypertrophy acting via the Janus kinase–signal transducers and activators of transcription (JAK–STAT3) signaling pathway (Serrano et al., 2008).”
BackgroundSchoenfeld, B. J. (2013) · Sports Medicine · doi:10.1007/s40279-013-0017-1 · Cited by 538
“Interleukin (IL)-6 is an early-stage myokine purported to influence satellite-cell mediated myonuclear accretion [130], and it has been postulated that exercise-induced metabolic stress may stimulate its production [132].”
BackgroundIL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration
Deng, B., Wehling-Henricks, M., Villalta, S. A., Wang, Y., & Tidball, J. G. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103180 · Cited by 472
“However, the relationships between IL-6 and myoblast proliferation and differentiation are complex; IL-6 is well established as a muscle mitogen (25) that plays a significant role in muscle fiber growth (42), but it can also induce muscle wasting (43).”
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Skeletal Muscle as Potential Central Link between Sarcopenia and Immune Senescence
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“Serrano et al. (2008) used IL-6 deficient mice to demonstrate a clear role for IL-6 in satellite cell proliferation, and in the regulation of skeletal muscle growth.”
MethodSaclier, M., Yacoub‐Youssef, H., Mackey, A. L., Arnold, L., Ardjoune, H., Magnan, M., Sailhan, F., Chelly, J., Pavlath, G. K., Mounier, R., et al. (2012) · Stem Cells · doi:10.1002/stem.1288 · Cited by 446
Exercise Attenuates the Major Hallmarks of Aging
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Versatile functions for IL-6 in metabolism and cancer
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STAT3 signaling controls satellite cell expansion and skeletal muscle repair
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Cellular dynamics in the muscle satellite cell niche
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Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations
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“IL-6 is important for hypertrophic muscle growth and myogenesis in mice (Serrano et al. 2008).”
The myocardial JAK/STAT pathway: From protection to failure
Boengler, K., Hilfiker‐Kleiner, D., Drexler, H., Heusch, G., & Schulz, R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.08.002 · Cited by 373
Satellite cells in human skeletal muscle plasticity
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“IL-6 knock-out mice show a blunted muscle fiber hypertrophic response and less satellite cell mediated myonuclear accretion compared to wild-type mice following overload induced muscle hypertrophy (Serrano et al., 2008).”
BackgroundInfluentialNF-κB–mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia
He, W. A., Berardi, E., Cardillo, V. M., Acharyya, S., Aulino, P., Thomas-Ahner, J., Wang, J., Bloomston, M., Muscarella, P., Nau, P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68523 · Cited by 357
“The accretion of myoblasts to preexisting myofibers is essential for hypertrophic muscle growth (57–59).”
Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise
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Madaro, L., Passafaro, M., Sala, D., Etxaniz, U., Lugarini, F., Proietti, D., Alfonsi, M. V., Nicoletti, C., Gatto, S., De Bardi, M., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0151-y · Cited by 310
Regeneration of skeletal muscle
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“Interleukin-6 (IL-6) has also been revealed to play a role in progenitor cell recruitment (Al-Shanti et al. 2008; Wang et al. 2008) with Serrano et al. (2008) showing that elimination of IL-6 greatly diminishes muscle growth.”
BackgroundInterleukin 6 as an Energy Allocator in Muscle Tissue
Kistner, T. M., Pedersen, B. K., & Lieberman, D. E. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00538-4 · Cited by 295
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Pillon, N. J., Bilan, P. J., Fink, L. N., & Klip, A. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00553.2012 · Cited by 299
“Thus, IL-6 may have a newly appreciated role in the early inflammatory response induced by muscle injury in addition to its well-known role in satellite cell proliferation and muscle tissue hypertrophy(130, 165).”
BackgroundIlich, J. Z., Kelly, O. J., Inglis, J. E., Panton, L. B., Duque, G., & Ormsbee, M. J. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.02.007 · Cited by 282
“, 2011), indicating it is necessary for atrophy reversal, and perhaps satellite cell proliferation (Serrano et al., 2008).”
Zhang, C., Li, Y., Wu, Y., Wang, L., Wang, X., & Du, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419788 · Cited by 279
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Inflammation induced loss of skeletal muscle
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InfluentialOversecretion of interleukin-15 from skeletal muscle reduces adiposity
Quinn, L. S., Anderson, B. G., Strait-Bodey, L., Stroud, A. M., & Argilés, J. M. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90506.2008 · Cited by 267
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BackgroundBilski, J., Pierzchalski, P., Szczepanik, M., Bonior, J., & Zoladz, J. A. (2022) · Cells · doi:10.3390/cells11010160 · Cited by 271
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Saclier, M., Cuvellier, S., Magnan, M., Mounier, R., & Chazaud, B. (2013) · FEBS Journal · doi:10.1111/febs.12166 · Cited by 270
Contractile C2C12myotube model for studying exercise-inducible responses in skeletal muscle
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Belizário, J. E., Fontes-Oliveira, C. C., Borges, J. P., Kashiabara, J. A., & Vannier, E. (2016) · SpringerPlus · doi:10.1186/s40064-016-2197-2 · Cited by 244
Fibro–Adipogenic Progenitors Cross-Talk in Skeletal Muscle: The Social Network
Biferali, B., Proietti, D., Mozzetta, C., & Madaro, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01074 · Cited by 257
The role of exercise-induced myokines in regulating metabolism
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“Along with its anti-inflammatory effect, myotube-produced IL-6 regulates satellite cell-mediated hypertrophic muscle growth (Serrano et al. 2008), induces glycogen breakdown and lipolysis via AMPK (Kelly et al.”
BackgroundEffects of resistance training on the inflammatory response
Calle, M. C., & Fernández, M. L. (2010) · Nutrition Research and Practice · doi:10.4162/nrp.2010.4.4.259 · Cited by 247
“IL-6 has been shown to mediate hypertrophic muscle growth both in vitro and in vivo studies [60].”
BackgroundDoes Exercise-Induced Muscle Damage Play a Role in Skeletal Muscle Hypertrophy?
Schoenfeld, B. J. (2012) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e31824f207e · Cited by 258
IL-7 is expressed and secreted by human skeletal muscle cells
Haugen, F., Norheim, F., Lian, H., Wensaas, A. J., Dueland, S., Berg, O., Funderud, A., Skålhegg, B. S., Raastad, T., & Drevon, C. A. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00094.2009 · Cited by 237
“For example, in accordance with a previous study (40), we could not detect altered mRNA expression of IL-6 during myogenesis, indicating that full differentiation is not necessary for secretion of IL-6.”
BackgroundResultLatroche, C., Weiss‐Gayet, M., Muller, L., Gitiaux, C., Leblanc, P., Liot, S., Larbi, S. B., Abou-Khalil, R., Verger, N., Bardot, P., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.027 · Cited by 234
“Oncostatin M is a member of the gp130/IL-6 cytokine family and exerts pleiotropic effects through OSM receptor (OSMR) in mouse and OSMR and leukemia inhibitory factor receptor in human.”
BackgroundInfluentialCurrent Progress in Sports Genomics
Ahmetov, I. I., & Fedotovskaya, O. N. (2015) · Advances in clinical chemistry · doi:10.1016/bs.acc.2015.03.003 · Cited by 219
Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion
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Fibro-adipogenic progenitors in skeletal muscle homeostasis, regeneration and diseases
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“IL-6 promotes muscle stem cell proliferation and myogenic progression [73,74].”
BackgroundAdaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission
Sandonà, D., Desaphy, J., Camerino, G. M., Bianchini, E., Ciciliot, S., Danieli‐Betto, D., Dobrowolny, G., Furlan, S., Germinario, E., Goto, K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033232 · Cited by 191
“Also, the IL-6 gene deletion has been recently shown to blunt muscle hypertrophy [34] and delay recovery of gastrocnemius muscle from hindlimb unloading atrophy, suggesting a protective role of the interleukin in disuse atrophy [35].”
BackgroundMikkelsen, U. R., Langberg, H., Helmark, I. C., Skovgaard, D., Andersen, L. L., Kjær, M., & Mackey, A. L. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00707.2009 · Cited by 185
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“In mammals another cytokine, interleukin-6 (IL-6), which is locally and transiently produced by growing myofibres and associated satellite cells is involved in muscle fibre hypertrophy (Serrano et al., 2008).”
InfluentialPeake, J. M., Gatta, P. A. D., & Cameron‐Smith, D. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00467.2009 · Cited by 195
“IL-6 does not play an acute role in repairing muscle injury (161), but it is involved in muscle hypertrophy (1, 138).”
BackgroundInfluentialNorheim, F., Raastad, T., Thiede, B., Rustan, A. C., Drevon, C. A., & Haugen, F. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00326.2011 · Cited by 180
“Furthermore, muscle-produced IL-6 is important for hypertrophic skeletal muscle growth (40).”
Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism
Baht, G., Bareja, A., Lee, D. E., Rao, R. R., Huang, R., Huebner, J., Bartlett, D. B., Hart, C., Gibson, J. R., Lanza, I., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0184-y · Cited by 168
Role of satellite cells in muscle growth and maintenance of muscle mass
Pallafacchina, G., Blaauw, B., & Schiaffino, S. (2012) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2012.02.002 · Cited by 189
Divergent Roles of Inflammation in Skeletal Muscle Recovery From Injury
Howard, E. E., Pasiakos, S. M., Blesso, C. N., Fussell, M. A., & Rodriguez, N. R. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00087 · Cited by 187
Exercise and regulation of adipokine and myokine production
(2015) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2015.07.002 · Cited by 168
Cytokine and hormone responses to resistance training
Izquierdo, M., Ibañez, J., Calbet, J. A. L., Navarro-Amézqueta, I., González‐Izal, M., Idoate, F., Häkkinen, K., Kraemer, W. J., Palacios-Sarrasqueta, M., Almar, M., et al. (2009) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1139-x · Cited by 164
“Interleukin-6 (IL-6) is locally produced by growing myoWbers and acts as an essential regulator of satellite cell (muscle stem cell)-mediated hypertrophic muscle growth (Hiscock et al. 2004; Keller et al. 2001; Penkowa et al. 2003; Serrano et al. 2008; Vierck et al. 2000).”
BackgroundROS and myokines promote muscle adaptation to exercise
Schéele, C., Nielsen, S. J., & Pedersen, B. K. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.12.002 · Cited by 169
Michailidis, Y., Karagounis, L., Terzis, G., Jamurtas, A., Spengos, K., Tsoukas, D., Chatzinikolaou, A., Mandalidis, D., Stefanetti, R., Papassotiriou, I., et al. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.049163 · Cited by 166
“IL-6 may be essential for myoblast proliferation and muscle growth (1, 41), whereas IL-6 mutation impairs myogenesis (43).”
BackgroundMyokines mediate the cross talk between skeletal muscle and other organs
Chen, W., Wang, L., You, W., & Shan, T. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30033 · Cited by 162
Suga, T., Okita, K., Morita, N., Yokota, T., Hirabayashi, K., Horiuchi, M., Takada, S., Omokawa, M., Kinugawa, S., & Tsutsui, H. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00504.2009 · Cited by 162
“suggested to regulate muscle growth/hypertrophy (24, 28, 30).”
BackgroundER stress in skeletal muscle remodeling and myopathies
Afroze, D., & Kumar, A. (2017) · FEBS Journal · doi:10.1111/febs.14358 · Cited by 168
Skeletal muscle regeneration and impact of aging and nutrition
Domingues-Faria, C., Vasson, M.-P., Goncalves-Mendes, N., Boirie, Y., & Walrand, S. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2015.12.004 · Cited by 157
Fiore, D., Judson, R. N., Low, M., Lee, S., Erica, Z., Hopkins, C. I., Xu, P., Lenzi, A., Rossi, F. M. V., & Lemos, D. R. (2016) · Stem Cell Research · doi:10.1016/j.scr.2016.06.007 · Cited by 156
“…and IL6 present obvious candidates as they are both highly expressed in FAPs and have established roles in regulating satellite cells and muscle regeneration (Joe et al., 2010; Lemos et al., 2012; Zhang et al., 2013; Serrano et al., 2008; Strle et al., 2007; Deng et al., 2012; Judson et al., 2013).”
BackgroundRequirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy
Goh, Q., & Millay, D. P. (2017) · eLife · doi:10.7554/elife.20007 · Cited by 167
“, 2002) or through genetic manipulation of IL-6-dependent effects on SC/MP activity (Guerci et al., 2012; Serrano et al., 2008).”
BackgroundToth, K., McKay, B. R., Lisio, M. D., Little, J. P., Tarnopolsky, M. A., & Parise, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017392 · Cited by 159
“Importantly, IL-6 knockout mice demonstrated a blunted hypertrophic response and less SC-mediated myonuclear accretion compared to wild-type mice following compensatory hypertrophy [26].”
BackgroundInfluentialLIF is a contraction-induced myokine stimulating human myocyte proliferation
Broholm, C., Laye, M. J., Brandt, C., Vadalasetty, R., Pilegaard, H., Pedersen, B. K., & Scheele, C. C. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01399.2010 · Cited by 155
“Furthermore, it has become apparent that the production of cytokines and growth factors by skeletal muscle itself contributes to the regulation of muscle growth and metabolism (24, 29, 31).”
BackgroundRole of Interleukin-6 in Vascular Health and Disease
Villar-Fincheira, P., Sanhueza-Olivares, F., Norambuena-Soto, I., Cancino-Arenas, N., Hernandez-Vargas, F., Troncoso, R., Gabrielli, L., & Chiong, M. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.641734 · Cited by 154
“Because the secretion of IL-6 is also triggered by glucagon-like peptide 1, an incretin released by food intake (Shirazi et al., 2013), and IL-6 induces suppression of food intake and reduction of body weight, an interesting cross-talk between exercise and food consumption could exist through the…”
BackgroundLe Bihan, M.-C., Bigot, A., Jensen, S. S., Dennis, J. L., Rogowska-Wrzesinska, A., Lainé, J., Gache, V., Furling, D., Jensen, O. N., Voit, T., et al. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.09.008 · Cited by 153
“[7] Serrano AL, Baeza-Raja B, Perdiguero E, Jardi M, Munoz-Canoves P.”
Pathogenesis, classification and treatment of inflammatory myopathies
Zong, M., & Lundberg, I. E. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.39 · Cited by 153
“and cultured muscle fibers were found to release IL-6”
BackgroundMuscle-bone interactions: From experimental models to the clinic? A critical update
Laurent, M. R., Dubois, V., Claessens, F., Verschueren, S., Vanderschueren, D., Gielen, E., & Jardí, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.10.017 · Cited by 156
“Similarly, IL-6 is required for muscle hypertrophy and recovery from muscle atrophy (Serrano et al., 2008; Washington et al., 2011), but chronic direct IL-6 administration induces muscle atrophy (Haddad et al., 2005).”
BackgroundAn Overview About the Biology of Skeletal Muscle Satellite Cells
Forcina, L., Miano, C., Pelosi, L., & Musarò, A. (2019) · Current Genomics · doi:10.2174/1389202920666190116094736 · Cited by 155
McKay, B. R., De Lisio, M., Johnston, A. P. W., O'Reilly, C. E., Phillips, S. M., Tarnopolsky, M. A., & Parise, G. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006027 · Cited by 149
“IL-6, IL-6 receptor (IL-6Ra), cyclin D1, suppressor of cytokine signling-3 (SOCS3) mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit.”
BackgroundInfluentialPeake, J., Roberts, L., Figueiredo, V., Egner, I., Krog, S., Aas, S. N., Suzuki, K., Markworth, J. F., Coombes, J. S., Cameron-Smith, D., et al. (2017) · Journal of Physiology · doi:10.1113/jp272881 · Cited by 147
“2013) and regulating muscle repair (Broussard et al. 2004; Chen et al. 2007; Serrano et al. 2008; Yahiaoui et al. 2008; Zhang et al. 2013).”
BackgroundInfluentialFibroadipogenic progenitors are responsible for muscle loss in limb girdle muscular dystrophy 2B
Hogarth, M. W., Defour, A., Lazarski, C. A., Gallardo, E., Díaz‐Manera, J., Partridge, T. A., Nagaraju, K., & Jaiswal, J. K. (2019) · Nature Communications · doi:10.1038/s41467-019-10438-z · Cited by 147
Intramuscular mechanisms of overtraining
Cheng, A. J., Jude, B., & Lanner, J. T. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101480 · Cited by 176
Beneficial bacteria inhibit cachexia
Varian, B. J., Goureshetti, S., Poutahidis, T., Lakritz, J. R., Levkovich, T., Kwok, C., Teliousis, K., Ibrahim, Y. M., Mirabal, S., & Erdman, S. E. (2016) · Oncotarget · doi:10.18632/oncotarget.7730 · Cited by 146
“This matches earlier studies of cachexia in ApcMIN mice [7-10], and also other recent work showing that feeding of L.”
BackgroundResultMuscle stem cell isolation and in vitro culture for meat production: A methodological review
Choi, K., Yoon, J. W., Kim, M., Lee, H. J., Jeong, J., Ryu, M., Jo, C., & Lee, C. (2020) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12661 · Cited by 152
The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Moresi, V., Adamo, S., & Berghella, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00500 · Cited by 145
McElhaney, J. E., Kuchel, G. A., Zhou, X., Swain, S. L., & Haynes, L. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00041 · Cited by 142
“By contrast, IL-6 contributes to induction of skeletal muscle stem cell responses after exercise (96), while in its absence recovery from disuse atrophy (97) and overload-induced hypertrophy (98) are decreased.”
BackgroundGuerci, A., Lahoute, C., Hébrard, S., Collard, L., Graindorge, D., Favier, M., Cagnard, N., Batonnet‐Pichon, S., Précigout, G., García, L., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.001 · Cited by 152
“Compensatory hypertrophy (CH) of plantaris muscles was induced as described (Serrano et al., 2008).”
BackgroundMethodInfluentialMyostatin and its Regulation: A Comprehensive Review of Myostatin Inhibiting Strategies
Baig, M. H., Ahmad, K., Moon, J. S., Park, S.-Y., Ho Lim, J., Chun, H. J., Qadri, A. F., Hwang, Y. C., Jan, A. T., Ahmad, S. S., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.876078 · Cited by 135
Exercise-induced myokines in health and metabolic diseases
So, B., Kim, H., Kim, J., & Song, W. J. (2014) · Integrative Medicine Research · doi:10.1016/j.imr.2014.09.007 · Cited by 139
Fatouros, I., & Jamurtas, A. (2016) · Journal of Inflammation Research · doi:10.2147/jir.s114635 · Cited by 116
Regenerative function of immune system: Modulation of muscle stem cells
Saini, J., McPhee, J. S., Al-Dabbagh, S., Stewart, C. E., & Al‐Shanti, N. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.03.006 · Cited by 130
“IL-6-/- mice show slower rates of 300 hypertrophic muscle growth than wild-type animals (Serrano et al., 2008).”
BackgroundMechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance
Balakrishnan, R., & Thurmond, D. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094636 · Cited by 143
“Furthermore, muscle fiber-derived myokines are involved in the autocrine/paracrine regulation of satellite cells and promote muscle hypertrophy during exercise [19,20].”
BackgroundCytokine response of primary human myotubes in an in vitro exercise model
Scheler, M., Irmler, M., Lehr, S., Hartwig, S., Staiger, H., Al-Hasani, H., Beckers, J., Hrabé de Angelis, M., Häring, H.-U., & Weigert, C. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00043.2013 · Cited by 123
Systemic Nutrient and Stress Signaling via Myokines and Myometabolites
Rai, M., & Demontis, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105305 · Cited by 123
Begue, G., Douillard, A., Galbes, O., Rossano, B., Vernus, B., Candau, R., & Py, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057141 · Cited by 124
“(2008) have shown a blunted hypertrophic response in skeletal muscle of IL-6 mice following compensatory hypertrophy, suggesting that IL-6 may play a role in skeletal muscle hypertrophy [18].”
BackgroundInfluentialMaurel, D. B., Jähn, K., & Lara-Castillo, N. (2017) · Biomedicines · doi:10.3390/biomedicines5040062 · Cited by 127
“IL-6 from muscle regulates satellite cell (muscle stem cells) differentiation to mediate skeletal hypertrophy [27].”
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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