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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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Methenitis, S. K., Stergiou, I. Ε., Antonopoulou, S., & Nomikos, T. (2021) · Biomedicines · doi:10.3390/biomedicines9010036 · Cited by 23
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“In muscle, JAK/STAT activation is required for stem cell committal and progression to differentiation and muscle growth, yet sustained activation has deleterious effects on muscle regeneration via impaired stem cell expansion and muscle mass through the activation of proteasomal degradation pathway via C/EBPδ (Serrano…”
BackgroundLi, X., Du, W., Ma, F. X., Feng, X., Bayard, F., & Han, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128647 · Cited by 24
“IL-6 is involved in tissue damage repair and regeneration [16, 17] as well as immunosuppressive activities [8, 11, 12].”
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“, 2005) and induces muscle regeneration (Serrano et al., 2008).”
Changes in Communication between Muscle Stem Cells and their Environment with Aging
Thorley, M., Malatras, A., Duddy, W. J., Gall, L. L., Mouly, V., Butler-Browne, G. S., & Duguez, S. (2015) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-150097 · Cited by 25
“It has been shown to be an important regulator of muscle stem cells [53], as it activates janus kinase 2 (Jak2) that will in turn phosphorylate STAT3 [52].”
BackgroundEffects of Tofacitinib on Muscle Remodeling in Experimental Rheumatoid Sarcopenia
Bermejo-Álvarez, I., Pérez-Baos, S., Gratal, P., Medina, J. P., Largo, R., Herrero‐Beaumont, G., & Mediero, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713181 · Cited by 22
“As is well established, IL-6 is involved in hypertrophy [36]; it is induced by resistance exercise in human muscle, in electrically stimulated cultured human myotubes [37,38], and in control satellite cell proliferation [36].”
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Ziemkiewicz, N., Talovic, M., Madsen, J., Hill, L. K., Scheidt, R., Patel, A., Haas, G. J., Marcinczyk, M., Zustiak, S. P., & Garg, K. (2018) · Biomedical Materials · doi:10.1088/1748-605x/aad915 · Cited by 21
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“The activation of STAT3 in response to muscle injury and resistance exercise occurs due to the production of the IL-6 cytokine (17,19,20).”
BackgroundMinari, A. L. A., & dos Santos, R. V. T. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00038.2021 · Cited by 21
Neuronal Agrin Promotes Proliferation of Primary Human Myoblasts in an Age-Dependent Manner
Gros, K., Matkovič, U., Parato, G., Miš, K., Luin, E., Bernareggi, A., Sciancalepore, M., Marš, T., Lorenzon, P., & Pirkmajer, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911784 · Cited by 20
“Interestingly, AgFL did not alter the phosphorylation of STAT3 (at Tyr705) (Figure 2D), a transcription factor that plays an important role in myoblast proliferation [71,72] and differentiation [73,74], neither the phosphorylation of focal adhesion kinase (FAK; at Tyr397) (Figure 2E), which participates in the Lrp4-Mu…”
Backgroundda Silva, F. O. C., & de Macedo, D. V. (2011) · Brazilian Journal of Kinanthropometry and Human Performance · doi:10.5007/1980-0037.2011v13n4p320 · Cited by 30
Increased prevalence of MnSOD genetic polymorphism in endurance and power athletes
Ben‐Zaken, S., Eliakim, A., Nemet, D., Kassem, E., & Meckel, Y. (2013) · Free Radical Research · doi:10.3109/10715762.2013.838627 · Cited by 20
The Impact of Partial Vascular Occlusion on Oxidative Stress Markers during Resistance Exercise
Garten, R., Goldfarb, A. H., Crabb, B., & Waller, J. D. (2015) · International Journal of Sports Medicine · doi:10.1055/s-0034-1396827 · Cited by 20
Velleman, S. G., Shin, J. S., Li, X., & Song, Y. Y. (2012) · Canadian Journal of Animal Science · doi:10.4141/cjas2011-098 · Cited by 20
BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise
Guo, M., Shen, F., Guo, X., Zhang, J., Ma, Y., Wu, X., Zuo, H., Yao, J., Hu, Y., Wang, D., et al. (2024) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2024.100968 · Cited by 21
“7A and 7C), as well as potentiated downstream effector genes for muscle hypertrophy, including IL-6 10,64 (Fig.”
Čurović, I. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1549609 · Cited by 23
The Impact of CB1 Receptor on Inflammation in Skeletal Muscle Cells
Haddad, M. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s322247 · Cited by 20
Yamamoto, A., Honda, S., Ogura, M., Kato, M., Tanigawa, R., Fujino, H., & Kawamoto, S. (2022) · Nutrients · doi:10.3390/nu14051078 · Cited by 20
“reported that compensatory hypertrophy increased IL-6 mRNA and IL-6 protein expression in the muscle of normal mice and that IL-6 knockout mice exhibited blunted muscle hypertrophy and suppressed SC activation and proliferation following compensatory hypertrophy [30].”
BackgroundInfluentialImpact of cancer cachexia on respiratory muscle function and the therapeutic potential of exercise
Murphy, B. T., Mackrill, J. J., & O’Halloran, K. D. (2022) · The Journal of Physiology · doi:10.1113/jp283569 · Cited by 20
“Additionally, IL-6 is implicated in the mediation of muscle growth (Serrano et al., 2008).”
BackgroundFennel, Z. J., Bourrant, P., Kurian, A., Petrocelli, J. J., de Hart, N. M. M. P., Yee, E. M., Boudina, S., Keirstead, H. S., Nistor, G., Greilach, S. A., et al. (2024) · Aging Cell · doi:10.1111/acel.14144 · Cited by 20
“In agreement, muscle-derived IL-6 can mediate adaptations including hypertrophy (Serrano et al., 2008) and lipolysis (Wolsk et al., 2010) in skeletal muscle as well as lipolysis (van Hall et al., 2003) and metabolic reprograming (Li et al., 2021) in”
BackgroundLombardi, G., Barbaro, M., Locatelli, M., & Banfi, G. (2017) · Endocrine · doi:10.1007/s12020-017-1239-z · Cited by 19
Deyhle, M. R., Hafen, P. S., Parmley, J., Preece, C. N., Robison, M., Sorensen, J. R., Jackson, B., Eggett, D. L., Hancock, C. R., & Hyldahl, R. D. (2018) · Physiological Reports · doi:10.14814/phy2.13689 · Cited by 19
“This is the case with IL-6, as it is dispensable for muscle regeneration but it is needed for muscle hypertrophy following synergist ablation (Serrano et al. 2008).”
BackgroundKnuiman, P., Hopman, M. T. E., Hangelbroek, R., & Mensink, M. (2018) · Physiological Reports · doi:10.14814/phy2.13708 · Cited by 18
Carmody, C., Ogawa-Wong, A. N., Martin, C., Luongo, C., Zuidwijk, M. J., Sager, B., Petersen, T., Guetter, A. R., Janssen, R., Wu, E. Y., et al. (2019) · Endocrinology · doi:10.1210/en.2019-00088 · Cited by 17
Satellite cell activation and number following acute and chronic exercise: A mini review
Martin, N. R., & Lewis, M. P. (2012) · Cellular and Molecular Exercise Physiology · doi:10.7457/cmep.v1i1.e3 · Cited by 20
“Indeed, O’Reilly et al. (2008) found that there was a slight trend towards an increase in muscle HGF following exercise, although not significant, whereas there was a significant increase in serum HGF concentrations (O'Reilly et al., 2008, Serrano et al., 2008).”
BackgroundFilippi, M., MOCK, D., Fuentes, J., Michelis, M. Y., Balciunaite, A., Paniagua, P., Hopf, R., Barteld, A., Eng, S., Badolato, A., et al. (2025) · Science Advances · doi:10.1126/sciadv.adv2628 · Cited by 18
“During skeletal muscle development, IL-6 plays a crucial role in satellite cell activation, myoblast proliferation, and subsequent differentiation into mature myotubes ( 30 , 32 ).”
Physical Activity, Obesity and Weight Loss Maintenance
Brandt, C., & Pedersen, B. K. (2022) · Handbook of experimental pharmacology · doi:10.1007/164_2021_575 · Cited by 21
Cancer Cachexia: Signaling and Transcriptional Regulation of Muscle Catabolic Genes
Rao, V. K., Das, D., & Taneja, R. (2022) · Cancers · doi:10.3390/cancers14174258 · Cited by 21
“These findings highlight a context-dependent role for IL-6 in muscle growth [69].”
BackgroundHORSE SPECIES SYMPOSIUM: The aging horse: Effects of inflammation on muscle satellite cells
Reed, S. A., LaVigne, E. K., Jones, A. K., Patterson, D. F., & Schauer, A. L. (2014) · Journal of Animal Science · doi:10.2527/jas.2014-8448 · Cited by 18
Sente, T., Berendoncks, A. M. V., Jonckheere, A. I., Rodenburg, R. J., Lauwers, P., Hoof, V. O. V., Wouters, A., Lardon, F., Hoymans, V. Y., & Vrints, C. J. (2016) · BMC Cardiovascular Disorders · doi:10.1186/s12872-016-0278-3 · Cited by 18
“and migration become attenuated, leading to a reduction in myofiber size [29].”
BackgroundInsights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin
Forcina, L., Pelosi, L., Miano, C., & Musarò, A. (2017) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk2040044 · Cited by 18
“Indeed, IL-6 is locally and transiently produced in response to exercise and injury, and it plays an important role in satellite cell proliferation and muscle growth [52,53].”
BackgroundGuerci, A., & Sotiropoulos, A. (2012) · BioArchitecture · doi:10.4161/bioa.20699 · Cited by 18
Zhong, P., Li, X., & Li, J. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1551561 · Cited by 18
“In addition to its direct effects on SCs, IL-6 promotes cell proliferation via paracrine signaling (173).”
Wright, C. R., Brown, E. L., Gatta, P. A. D., Fatouros, I. G., Karagounis, L. G., Terzis, G. D., Mastorakos, G., Michailidis, Y., Mandalidis, D. G., Spengos, K., et al. (2015) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2014.0159 · Cited by 17
Muscle stem cell aging: identifying ways to induce tissue rejuvenation
Sousa‐Victor, P., Neves, J., & Muñoz‐Cánoves, P. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111246 · Cited by 18
Self-citationvan Santen, V. J. B., Klein‐Nulend, J., Bakker, A. D., & Jaspers, R. T. (2022) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-021-01050-4 · Cited by 19
“Il-6 stimulates myoblast proliferation and differentiation by activating STAT3 and the expression of its target genes SOCS3 and Cyclin D1 [49].”
BackgroundWing, M. R., Yang, W. P., Teal, V. L., Navaneethan, S. D., Tao, K., OJO, A. O., Guzmán, N., Reilly, M. P., Wolman, M., Rosas, S. E., et al. (2014) · Obesity · doi:10.1002/oby.20692 · Cited by 17
“Besides its well-recognized role in mediating muscle protein catabolism, cytokines are also essential for successful muscle regeneration (10,26).”
BackgroundShultz, S. P., Dahiya, R., Leong, G. M., ROWLANDS, D. S., Hills, A. P., & Byrne, N. M. (2015) · Australasian Medical Journal · doi:10.4066/amj.2015.2293 · Cited by 17
Alheib, O., da Silva, L. D., Kwon, I., Reis, R., & Correlo, V. (2022) · Trends in Biotechnology · doi:10.1016/j.tibtech.2022.09.010 · Cited by 16
Murphy, K. T., Allen, A. M., Chee, A., Naim, T., & Lynch, G. S. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00007.2012 · Cited by 16
“IL-6, TNF- , and IFN- were chosen as markers of inflammation and regeneration because TNF- and IFN- are involved in macrophage activation (12, 44) and all three cytokines stimulate muscle cell proliferation (12, 40, 44) and are involved in mediating ANG II-induced muscle wasting (17, 46, 49).”
BackgroundCytokine Mediated Control of Muscle Stem Cell Function
Joanisse, S., & Parise, G. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-27511-6_2 · Cited by 17
Boutrup, R. J., Farup, J., Vissing, K., Kjær, M., & Mikkelsen, U. R. (2018) · Rheumatology International · doi:10.1007/s00296-018-4028-y · Cited by 16
IL-6 Blockade as a Therapeutic Approach for Duchenne Muscular Dystrophy
Mammen, A. L., & Sartorelli, V. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.03.018 · Cited by 16
“Third, in addition to promoting a potentially harmful inflammatory milieu, IL-6 has also been reported to play a role in muscle regeneration by promoting myoblast differentiation (Serrano et al., 2008); any therapeutic intervention aimed at blocking IL-6 in humans should consider this dual role of IL-6.”
BackgroundSeo, E., Kang, H., Lim, O.-K., & Jun, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061557 · Cited by 16
“cell-cycle-associated genes such as cyclin D1 and c-myc and stimulates muscle growth through IL-4, which promotes myoblast fusion [41,49].”
BackgroundTalović, M., Patel, K. H., Schwartz, M. A., Madsen, J., & Garg, K. (2019) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2933 · Cited by 16
Schroer, A. B., Mohamed, J. S., Willard, M. D., Setola, V., Oestreich, E. A., & Siderovski, D. P. (2019) · PLoS ONE · doi:10.1371/journal.pone.0216167 · Cited by 16
Winchester, L. J., Morris, C. E., Badinger, J., Wiczynski, T., & VanWye, W. R. (2020) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003742 · Cited by 17
“demonstrated that enhanced IL-6 expression after exercise is pivotal for inducing satellite cell mobilization and proliferation, a prominent mechanism of muscular hypertrophy (33).”
BackgroundLoh, K. C., Leong, W.-I., Carlson, M. E., Oskouian, B., Kumar, A., Fyrst, H., Zhang, M., Proia, R. L., Hoffman, E. P., & Saba, J. D. (2012) · PLoS ONE · doi:10.1371/annotation/7e7ac57d-30ae-4e49-9138-e3bdbe3491d2 · Cited by 16
Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs
Renzini, A., D’Onghia, M., Coletti, D., & Moresi, V. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.706003 · Cited by 15
“Studies conducted in mice and humans highlighted that in response to physical exercise IL-6 exerts a positive role in modulating muscle mass, insulin secretion and lipid metabolism (Rosendal et al., 2005; Serrano et al., 2008; Ellingsgaard et al., 2011; da Silva Vasconcelos and Fernanda Salla, 2018).”
BackgroundThe inflammatory response, a mixed blessing for muscle homeostasis and plasticity
Bouredji, Z., Argaw, A., & Frenette, J. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1032450 · Cited by 19
“IL-6 is an essential regulator of satellite cell-mediated muscle growth while the deletion of the IL-6 gene attenuates muscle hypertrophy and reduces the proliferation of satellite cells via STAT3 as well as the expression of its target, cyclin D1 (Serrano et al., 2008).”
BackgroundStromal vascular fraction in the treatment of myositis
Gandolfi, S., Pileyre, B., Drouot, L., Dubus, I., Auquit-Auckbur, I., & Martinet, J. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01605-9 · Cited by 17
“After activation and differentiation, FAP are another source of myogenic factor like Wnt family members, IL-6 and Insulin-like Grow-Factor 1 (IGF1), which enhance satellite cell proliferation and myoblast differentiation and fusion [33 – 35].”
BackgroundHan, L., Li, P., He, Q., Yang, C. G., Jiang, M., Wang, Y., Cao, Y., Han, X., Liu, X., & Wu, W. (2023) · Aging and Disease · doi:10.14336/ad.2023.1125 · Cited by 17
HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration
Peng, H., Chen, K., Huang, B., Liu, M., Cui, M., Rozenberg, I., Chaqour, B., Pan, X., Barton, E. R., Jiang, X.-C., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62818 · Cited by 15
“Furthermore, upon treatment with IL-6, an activator of satellite cell proliferation (47), HEXIM1 was released from P-TEFb complexes more rapidly in Hexim1 +/– cultures than in WT controls (Figure 8G).”
Lombardi, G., Sansoni, V., & Banfi, G. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2017.07.11 · Cited by 17
“It is independent of TNF-α (83) and it is not associated with myocyte damage (76) but it drives muscle regeneration and recovery from atrophy (84,85).”
Backgroundda Rocha, F. D., Haupenthal, D. P. D. S., Zaccaron, R., Corrêa, M. E. A. B., Tramontin, N. D. S., Fonseca, J. P., Nesi, R. T., Muller, A., Pinho, R. A., Paula, M. M. D. S., et al. (2020) · Journal of drug targeting (Print) · doi:10.1080/1061186x.2019.1652617 · Cited by 11
“The cytokines further promote the migration, proliferation, and survival of various cell types at the injury site, whereas the inflammatory cells are responsible for the phagocytosis of cell debris [9,10].”
BackgroundMallinson, J. E., Taylor, T., Constantin‐Teodosiu, D., Billeter-Clark, R., Constantin, D., Franchi, M. V., Narici, M. V., Auer, D. P., & Greenhaff, P. L. (2020) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.13791 · Cited by 17
Muscle growth in young horses: Effects of age, cytokines, and growth factors1
LaVigne, E. K., Jones, A. K., Londoño, A. S., Schauer, A., Patterson, D. F., Nadeau, J., & Reed, S. A. (2015) · Journal of Animal Science · doi:10.2527/jas.2015-9634 · Cited by 15
Zembroń-Łacny, A., Gajewski, M., Naczk, M., Dziewiecka, H., & Siatkowski, I. (2012) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-012-0221-8 · Cited by 15
“The genetic loss of IL-6 blunts the muscle regeneration and hypertrophy in vivo [20].”
BackgroundIs Postexercise Muscle Soreness a Valid Indicator of Muscular Adaptations?
Schoenfeld, B. J., & Contreras, B. M. (2013) · Strength and conditioning journal · doi:10.1519/ssc.0b013e3182a61820 · Cited by 15
“Myokines have been shown to possess anabolic properties, exerting their effects in an autocrine/paracrine fashion to bring about unique effects on skeletal muscle adaptation (36,43,51).”
BackgroundShin, J., Méndez-López, I., Hong, M., Wang, Y., Tanji, K., Wu, W., Shugol, L., Krauss, R. S., Dauer, W. T., & Worman, H. J. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw368 · Cited by 15
Khan, M. A. S., Khan, M. F., Kashiwagi, S., Kem, W. R., Yasuhara, S., Kaneki, M., Tompkins, R. G., & Martyn, J. A. J. (2017) · Shock · doi:10.1097/shk.0000000000000849 · Cited by 15
“IL-6, however, has also been identified as an essential regulator of satellite cellmediated hypertrophic muscle growth (6, 19).”
InfluentialIl-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblastsPreprint
Stauber, T., Moschini, G., Hussien, A. A., Jaeger, P. K., Bock, K. D., & Snedeker, J. G. (2023) · eLife · doi:10.7554/elife.87092 · Cited by 15
Arabzadeh, E., Shirvani, H., Zahmatkesh, M. E., Malayeri, S. R., Meftahi, G. H., & Rostamkhani, F. (2022) · 3 Biotech · doi:10.1007/s13205-022-03253-9 · Cited by 14
Spatial compartmentalization of signaling imparts source-specific functions on secreted factors
Groppa, E., Martini, P. G. V., Derakhshan, N., Théret, M., Ritso, M., Tung, L. W., Wang, Y. X., Soliman, H. S., Hamer, M. S., Stankiewicz, L. N., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112051 · Cited by 15
Post-natal muscle growth and protein turnover: a narrative review of current understanding
Millward, D. J. (2023) · Nutrition Research Reviews · doi:10.1017/s0954422423000124 · Cited by 15
Musgrove, L., Russell, F. D., & Ventura, T. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2342480 · Cited by 14
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“IL-6 [4,7,23,28,36,37,39–41] It is involved in autocrine and paracrine signaling in skeletal muscle, particularly activating the STAT3 pathway, which is important for hypertrophic muscle growth and myogenesis.”
BackgroundTHE EFFECT OF CAFFEINE SUPPLEMENTATION ON TRAINED INDIVIDUALS SUBJECTED TO MAXIMAL TREADMILL TEST
Salício, V. A. M. M., AlexandreFett, C., Salício, M. A., Fernanda, C., MoraesBrandão, C. C., Stoppiglia, L. F., & Fett, W. C. R. (2016) · African Journal of Traditional Complementary and Alternative Medicines · doi:10.21010/ajtcam.v14i1.3 · Cited by 14
“Accordingly, IL-6 has shown an effect that may be associated with the recovery process of skeletal muscle contraction in some studies about myokine (Moldoveanu et al, 2001; Serrano et al, 2008).”
BackgroundSilva, P. A. R. E., Neves, A. D. C., da Rocha, C. B., Moura-da-Silva, A. M., & Faquim-Mauro, E. L. (2019) · Inflammation · doi:10.1007/s10753-019-01016-y · Cited by 14
IL-6 and metabolism—new evidence and new questions
Krook, A. (2008) · Diabetologia · doi:10.1007/s00125-008-1019-7 · Cited by 16
“Recent work from Muñoz-Cánoves’ group highlights that IL-6 is an essential regulator of satellite cell-mediated hypertrophic muscle growth [15].”
BackgroundAgostinete, R. R., Rossi, F. E., Magalhães, A. J. B., Rocha, A. P. R., Parmezzani, S. S., Gerosa-Neto, J., Cholewa, J. M., & Lira, F. S. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00444 · Cited by 14
“IL-6 initiates the recovery process by modulating muscle regulatory genes (i.e., MyoD; Warren et al., 2002; Gleeson and Bishop, 2005; Tidball, 2005) and activating muscle satellite cells (Serrano et al., 2008), and therefore may play a role in the hypertrophic process.”
BackgroundToll-like receptor ligand-dependent inflammatory responses in chick skeletal muscle myoblasts
Nihashi, Y., Ono, T., KAGAMI, H., & Takaya, T. (2018) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2018.10.013 · Cited by 15
Effect of eccentric contraction on satellite cell activation in human vastus lateralis muscle
Imaoka, Y., Kawai, M., Mori, F., & Miyata, H. (2015) · The Journal of Physiological Sciences · doi:10.1007/s12576-015-0385-4 · Cited by 14
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“There seems to be a delicate balance as the proinflammatory cytokine response to exercise plays an important role in initiating muscle repair and remodeling (Hawke & Garry, 2001; Mackey et al., 2007; Serrano et al., 2008).”
BackgroundResultGjevestad, G. O., Hamarsland, H., Raastad, T., Ottestad, I. O., Christensen, J. J., Eckardt, K., Drevon, C. A., Biong, A. S., Ulven, S. M., & Holven, K. B. (2017) · Genes & Nutrition · doi:10.1186/s12263-017-0556-4 · Cited by 14
Chen, P., Hsu, C.-C., Lai, L.-F., Chi, C.-P., & Yu, S.-H. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.824210 · Cited by 13
Hormonal, immune, and oxidative stress responses to blood flow‐restricted exercise
Hjortshoej, M. H., Aagaard, P., Storgaard, C. D., Juneja, H., Lundbye‐Jensen, J., Magnusson, S. P., & Couppé, C. (2023) · Acta Physiologica · doi:10.1111/apha.14030 · Cited by 13
Orthogonalized human protease control of secreted signals
Aldrete, C. A., Call, C. C., Sant’Anna, L. E., Vlahos, A. E., Pei, J., Cong, Q., & Gao, X. J. (2025) · Nature Chemical Biology · doi:10.1038/s41589-024-01831-x · Cited by 14
Orioli, L., & Thissen, J. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1554617 · Cited by 17
“IL-6 is produced transiently by growing muscle fi bers and satellite cells (151).”
MyD88 and TRIF mediate divergent inflammatory and regenerative responses to skeletal muscle ischemia
Sachdev, U., Cui, X. D., Xu, J. M., Xu, J., & Tzeng, E. (2014) · Physiological Reports · doi:10.14814/phy2.12006 · Cited by 13
“IL-6 has defined roles in muscle physiology and is released during strenuous exercise (Steensberg et al. 2002; Haddad et al. 2005; Serrano et al. 2008; McKay et al. 2009; Kobara et al. 2010).”
BackgroundKono, Y., Takegaki, J., Ohba, T., Matsuda, K., Negoro, R., Fujita, S., & Fujita, T. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120298 · Cited by 13
A Coupled Mechanobiological Model of Muscle Regeneration In Cerebral Palsy
Khuu, S., Fernandez, J. W., & Handsfield, G. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.689714 · Cited by 8
“This method simulates the behavior of chemical factors that attract macrophages (Serrano et al., 2008;Muñoz-Cánoves et al., 2013).”
MethodEffects of losartan and exercise on muscle mass and exercise endurance of old mice
Lin, C.-H., Chang, P., Chu, P., Chuang, Y., Huang, R., & Chen, C. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111869 · Cited by 13
Fndc5/irisin is regulated by myogenesis stage, irisin, muscle type and training.
Lavi, G., Horwitz, A., Einstein, O., Zipori, R., Gross, O., & Birk, R. Z. (2022) · PubMed Central · Cited by 13
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“IL6 is a multifunctional cytokine that might be also involved in muscle regeneration (Serrano et al., 2008).”
BackgroundSerra, M. C., Beavers, K. M., Beavers, D. P., & Willoughby, D. S. (2012) · Nutrition and Health · doi:10.1177/0260106012467243 · Cited by 13
“However, recent data have shown that higher systemic levels of IL-6 result in a down-regulation of IL-6 expressed in muscle (Serrano et al., 2008).”
BackgroundRegulation of muscle plasticity and trophism by fatty acids: A short review
Abreu, P., Leal‐Cardoso, J. H., Ceccatto, V. M., & Hirabara, S. M. (2017) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.63.02.148 · Cited by 13
“150 rEv assoc mEd Bras 2017; 63(2):148-155 leucine during the muscle regeneration process accelerates the repair of connective tissue in the anterior tibial muscle of rats.”
BackgroundInfluentialEpigenetics of Skeletal Muscle Aging
Sharples, A. P., Seaborne, R. A. E., & Stewart, C. E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-811060-7.00019-x · Cited by 14
Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy
Yoon, J. H., Lee, S.-M., Lee, Y., Kim, M. J., Yang, J. W., Choi, J. Y., Kwak, J. Y., Lee, K., Yang, Y. R., & Kwon, K. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.11.076 · Cited by 13
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“cachexia [29–31], although it was also reported that low levels of IL-6 could promote activation of satellite cells and myotube regeneration [32, 33].”
BackgroundP2Y1R and P2Y2R: potential molecular triggers in muscle regeneration
Wang, M., Yang, B., Jing, X.-Y., Wang, Y., Lu, K., Ren, K., & Kang, L. (2022) · Purinergic Signalling · doi:10.1007/s11302-022-09885-z · Cited by 12
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“SMSCs are myogenic stem cells that can provide new nuclei to support hypertrophy and regeneration of postnatal muscle through synthesizing muscle protein [13].”
BackgroundAre There Limitations to Exercise Benefits in Peripheral Arterial Disease?
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“IL-6 was suggested to promote muscle hypertrophy through STAT3, signal transducer and activator of transcription 3 signaling (34) while LIF, a”
BackgroundHidaka, K., Mikuni‐Takagaki, Y., Wada-Takahashi, S., Saita, M., Kawamata, R., Sato, T., Kawata, A., Miyamoto, C., Maehata, Y., Watabe, H., et al. (2019) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2019.02.015 · Cited by 15
Does exercise-induced apelin affect sarcopenia? A systematic review and meta-analysis
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“Exercise-induced myokines are observed to have a positive effect on glucose uptake and tolerance [5–7], fat oxidation [5, 8], and satellite cell proliferation [9, 10] and also to stimulate AMP-activated protein kinase signaling to increase glucose uptake and improve lipolysis [11, 12].”
BackgroundA macrophage-derived adipokine supports skeletal muscle regeneration
Chazaud, B. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0186-9 · Cited by 12
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“In a similar capacity, IL6 acts as a regulator to inflammatory effects, has been critically found to contribute to skeletal muscle growth during exercise, acting as a myokine, where it is continuously secreted via remodeling myoblasts, culminating in a 100-fold normal blood-borne increase, and bringing about hypertrop…”
BackgroundMethodPCM1 labeling reveals myonuclear and nuclear dynamics in skeletal muscle across species
Viggars, M. R., Owens, D. J., Stewart, C. E., Coirault, C., Mackey, A. L., & Jarvis, J. C. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00285.2022 · Cited by 12
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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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