JNK regulates muscle remodeling via myostatin/SMAD inhibition
Open accessAbstract
Skeletal muscle has a remarkable plasticity to adapt and remodel in response to environmental cues, such as physical exercise. Endurance exercise stimulates improvements in muscle oxidative capacity, while resistance exercise induces muscle growth. Here we show that the c-Jun N-terminal kinase (JNK) is a molecular switch that when active, stimulates muscle fibers to grow, resulting in increased muscle mass. Conversely, when muscle JNK activation is suppressed, an alternative remodeling program is initiated, resulting in smaller, more oxidative muscle fibers, and enhanced aerobic fitness. When muscle is exposed to mechanical stress, JNK initiates muscle growth via phosphorylation of the transcription factor, SMAD2, at specific linker region residues leading to inhibition of the growth suppressor, myostatin. In human skeletal muscle, this JNK/SMAD signaling axis is activated by resistance exercise, but not endurance exercise. We conclude that JNK acts as a key mediator of muscle remodeling during exercise via regulation of myostatin/SMAD signaling.
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Mechanistic insights from cell and animal studies suggest that when muscle is subjected to mechanical stress, it can downregulate myostatin expression via pathways such as JNK-mediated phosphorylation of transcription factor Smad2.
“Mechanistic insights from cell and animal studies suggest that when muscle is subjected to mechanical stress, it can downregulate MSTN expression via pathways such as JNK-mediated phosphorylation of transcription factor Smad2 [55,57].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [57]
The Results section on muscle JNK activation reports that mechanical stretch activated JNK and SMAD2 phosphorylation, and the Discussion links JNK-mediated SMAD2 phosphorylation to inhibition of myostatin activity. The source does not show that this pathway downregulates MSTN expression; in the Results section on myostatin activity in vivo, myostatin mRNA expression was similar in JNK-knockout and control mice. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredExercise downregulates myostatin expression, with the magnitude of reduction depending on exercise mode, duration, and intensity.
“Exercise downregulates MSTN expression, with the magnitude of reduction depending on exercise mode, duration, and intensity.”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [57]
The Discussion (page unavailable) says resistance exercise inhibits myostatin activity through JNK/SMAD2 signaling more strongly than endurance exercise, supporting a difference by exercise mode. It does not show that exercise downregulates MSTN expression or that the magnitude of an expression reduction depends on duration or intensity. The Results section on JNK suppression (page unavailable) reports similar myostatin mRNA expression in the mouse groups it compared. (LLM, conf=0.86)
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Cites
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,548 · see citing works
Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member
McPherron, A. C., Lawler, A. M., & Lee, S.-J. (1997) · Nature · doi:10.1038/387083a0 · Cited by 4,013 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases
Pedersen, B. K., & Saltin, B. (2015) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12581 · Cited by 3,514 · see citing works
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359 · see citing works
Martin, L., Birdsell, L., Macdonald, N., Reiman, T., Clandinin, M. T., McCargar, L. J., Murphy, R. A., Ghosh, S., Sawyer, M. B., & Baracos, V. E. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.2722 · Cited by 2,698 · see citing works
Smad transcription factorsPreprint
Massagué, J., Seoane, J., & Wotton, D. (2005) · Genes & Development · doi:10.1101/gad.1350705 · Cited by 2,432 · see citing works
Blair, S. N. (1996) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1996.03540030039029 · Cited by 1,819 · see citing works
High-Intensity Strength Training in Nonagenarians: Effects on Skeletal Muscle
Fiatarone, M. A. (1990) · JAMA · doi:10.1001/jama.1990.03440220053029 · Cited by 1,593 · see citing works
Brüning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Hörsch, D., Accili, D., Goodyear, L. J., & Kahn, C. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80155-0 · Cited by 1,183 · see citing works
Self-citationHuman Smad3 and Smad4 Are Sequence-Specific Transcription Activators
Zawel, L. S., Dai, J. L., Buckhaults, P., Zhou, S., Kinzler, K. W., Vogelstein, B., & Kern, S. E. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80061-1 · Cited by 940 · see citing works
Bouchard, C., An, P., Rice, T., Skinner, J. S., Wilmore, J. H., Gagnon, J., Pérusse, L., Leon, A. S., & Rao, D. C. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.3.1003 · Cited by 875 · see citing works
Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size
Trendelenburg, A. U., Meyer, A., Rohner, D., Boyle, J., Hatakeyama, S., & Glass, D. J. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00105.2009 · Cited by 792 · see citing works
Interference of strength development by simultaneously training for strength and endurance.
Hickson, R. C. (1980) · European Journal of Applied Physiology and Occupational Physiology · doi:10.1007/bf00421333 · Cited by 753 · see citing works
Ruegsegger, G. N., & Booth, F. W. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029694 · Cited by 690 · see citing works
FIBER TYPES AND METABOLIC POTENTIALS OF SKELETAL MUSCLES IN SEDENTARY MAN AND ENDURANCE RUNNERS*
Saltin, B., Henriksson, J., Nygaard, E., Andersen, P. H., & Jansson, E. (1977) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1977.tb38182.x · Cited by 655 · see citing works
Smad2 and 3 transcription factors control muscle mass in adulthood
Sartori, R., Milan, G., Patron, M., Mammucari, C., Blaauw, B., Abraham, R., & Sandri, M. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00104.2009 · Cited by 517 · see citing works
Cell Signaling and Stress ResponsesPreprint
Hotamışlıgil, G. S., & Davis, R. J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006072 · Cited by 496 · see citing works
Self-citationLei, K., Nimnual, A. S., Zong, W., Kennedy, N. J., Flavell, R. A., Thompson, C. B., Bar‐Sagi, D., & Davis, R. J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4929-4942.2002 · Cited by 463 · see citing works
Self-citationSarcopenia, Cachexia and Aging: Diagnosis, Mechanisms and Therapeutic Options - A Mini-Review
Ali, S., & Garcia, J. M. (2014) · Gerontology · doi:10.1159/000356760 · Cited by 462 · see citing works
Peak power output predicts maximal oxygen uptake and performance time in trained cyclists
Hawley, J. A., & Noakes, T. D. (1992) · European Journal of Applied Physiology and Occupational Physiology · doi:10.1007/bf01466278 · Cited by 422 · see citing works
(2005) · PubMed · Cited by 354 · see citing works
Concurrent exercise training: do opposites distract?
Coffey, V. G., & Hawley, J. A. (2017) · The Journal of Physiology · doi:10.1113/jp272270 · Cited by 351 · see citing works
Self-citationVariability in Muscle Size and Strength Gain After Unilateral Resistance Training
Shrier, I. (2006) · Yearbook of Sports Medicine · doi:10.1016/s0162-0908(08)70354-4 · Cited by 348 · see citing works
Hickey, M. S., Carey, J. O., Azevedo, J. L., Houmard, J. A., Pories, W. J., Israel, R. G., & Dohm, G. L. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.3.e453 · Cited by 305 · see citing works
Myostatin and the control of skeletal muscle mass
Lee, S., & McPherron, A. C. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00004-0 · Cited by 273 · see citing works
Martineau, L. C., & Gardiner, P. F. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.2.693 · Cited by 259 · see citing works
Exercise Mimetics: Impact on Health and Performance
Fan, W., & Evans, R. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.022 · Cited by 188 · see citing works
Nyholm, B., Qu, Z., Kaal, A., Pedersen, S. B., Gravholt, C. H., Andersen, J. L., Saltin, B., & Schmitz, O. (1997) · Diabetes · doi:10.2337/diab.46.11.1822 · Cited by 181 · see citing works
TGF-β and the Smad signal transduction pathway
Mehra, A., & Wrana, J. L. (2002) · Biochemistry and Cell Biology · doi:10.1139/o02-161 · Cited by 175 · see citing works
Early Time Course of Akt Phosphorylation after Endurance and Resistance Exercise
CAMERA, D. M., EDGE, J., SHORT, M. J., HAWLEY, J. A., & COFFEY, V. G. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181d964e4 · Cited by 154 · see citing works
Self-citationSuppression of p53-dependent senescence by the JNK signal transduction pathway
Das, M., Jiang, F., Sluss, H. K., Zhang, C., Shokat, K. M., Flavell, R. A., & Davis, R. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707782104 · Cited by 143 · see citing works
Self-citationLatres, E., Pangilinan, J., Miloscio, L., Bauerlein, R., Na, E., Potocky, T. B., Huang, Y., Eckersdorff, M., Rafique, A., Mastaitis, J., et al. (2015) · Skeletal Muscle · doi:10.1186/s13395-015-0060-8 · Cited by 143 · see citing works
Endurance Exercise and the Regulation of Skeletal Muscle Metabolism
Booth, F. W., Ruegsegger, G. N., Toedebusch, R. G., & Yan, Z. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.016 · Cited by 125 · see citing works
Using Molecular Biology to Maximize Concurrent Training
Baar, K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0252-0 · Cited by 118 · see citing works
Hamada, K., Takuwa, N., Yokoyama, K. K., & Takuwa, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.11.6334 · Cited by 115 · see citing works
Structural basis for potency differences between GDF8 and GDF11
Walker, R. G., Czepnik, M., Goebel, E. J., McCoy, J. C., Vujić, A., Cho, M., Oh, J., Aykul, S., Walton, K. L., Schang, G., et al. (2017) · BMC Biology · doi:10.1186/s12915-017-0350-1 · Cited by 112 · see citing works
Hubal, M. J., Hoffman, E. P., Devaney, J. M., Gordish-Dressman, H., Kearns, A., Zambraski, E., & Clarkson, P. M. (2005) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200505001-00881 · Cited by 104 · see citing works
Rowe, G. C., Safdar, A., & Arany, Z. P. (2014) · Circulation · doi:10.1161/circulationaha.113.001590 · Cited by 104 · see citing works
Molecular Regulation of Exercise-Induced Muscle Fiber HypertrophyPreprint
Bamman, M. M., Roberts, B. M., & Adams, G. R. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029751 · Cited by 95 · see citing works
Aronson, D., Boppart, M. D., Dufresne, S. D., Fielding, R. A., & Goodyear, L. J. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9435 · Cited by 89 · see citing works
Self-citationMyostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle
Mouisel, É., Relizani, K., Mille-Hamard, L., Denis, R., Hourdé, C., Agbulut, O., Patel, K., Arandel, L., Morales-Gonzalez, S., Vignaud, A., et al. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00377.2013 · Cited by 89 · see citing works
Contractile Activity Stimulates the c-Jun NH2-terminal Kinase Pathway in Rat Skeletal Muscle
Aronson, D., Dufresne, S. D., & Goodyear, L. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.41.25636 · Cited by 86 · see citing works
Self-citationLessard, S. J., Rivas, D. A., Alves-Wagner, A. B., Hirshman, M. F., Gallagher, I. J., Constantin‐Teodosiu, D., Atkins, R. P., Greenhaff, P. L., Qi, N., Gustafsson, T. P., et al. (2013) · Diabetes · doi:10.2337/db13-0062 · Cited by 85 · see citing works
Self-citationPadhi, D., Higano, C. S., Shore, N. D., SIEBER, P. R., Rasmussen, E., & Smith, M. R. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1271 · Cited by 81 · see citing works
Han, M. S., Barrett, T., Brehm, M. A., & Davis, R. J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.008 · Cited by 74 · see citing works
Self-citationSmad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy
Tando, T., Hirayama, A., Furukawa, M., Sato, Y., Kobayashi, T., Funayama, A., Kanaji, A., Wu, H., Watanabe, R., Morita, M., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.680579 · Cited by 67 · see citing works
Smad linker region phosphorylation in the regulation of extracellular matrix synthesis
Burch, M. L., Zheng, W., & Little, P. J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0514-4 · Cited by 65 · see citing works
Selectively bred rat model system for low and high response to exercise training
Koch, L. G., Pollott, G. E., & Britton, S. L. (2013) · Physiological Genomics · doi:10.1152/physiolgenomics.00021.2013 · Cited by 60 · see citing works
Lucarelli, P., Schilling, M., Kreutz, C., Vlasov, A., Boehm, M. E., Iwamoto, N., Steiert, B., Lattermann, S., Wäsch, M., Stepath, M., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2017.11.010 · Cited by 60 · see citing works
Rennie, M. J., & Wilkes, E. (2005) · PubMed · Cited by 43 · see citing works
The Low‐fitness Phenotype as a Risk Factor: More Than Just Being Sedentary?
Church, T. S. (2009) · Obesity · doi:10.1038/oby.2009.387 · Cited by 43 · see citing works
Morel, C., Standen, C. L., Jung, D. Y., Gray, S., Ong, H., Flavell, R. A., Kim, J. K., & Davis, R. J. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00585-10 · Cited by 30 · see citing works
Self-citationExercise: Teaching myocytes new tricks
Powers, S. K. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00418.2017 · Cited by 27 · see citing works
Myostatin tilts the balance between skeletal muscle size, function and metabolism
Matsakas, A. (2014) · Experimental Physiology · doi:10.1113/expphysiol.2013.076422 · Cited by 5 · see citing works
Flagged first, then by citations
2 of the 57 references couldn’t be matched to a known paper.
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D’Hulst, G., Soro-Arnaiz, I., Masschelein, E., Veys, K., Fitzgerald, G., Smeuninx, B., Kim, S., Deldicque, L., Blaauw, B., Carmeliet, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13889-6 · Cited by 2,310 · see citing works
Physical Activity and Brain Health
Liegro, C. M. D., Schiera, G., Proia, P., & Liegro, I. D. (2019) · Genes · doi:10.3390/genes10090720 · Cited by 392 · see citing works
Exercise Metabolism and Adaptation in Skeletal Muscle
Smith, J. A. B., Murach, K. A., Dyar, K. A., & Zierath, J. R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00606-x · Cited by 342 · see citing works
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Roberts, M. D., McCarthy, J. J., Hornberger, T. A., Phillips, S. M., Mackey, A. L., Nader, G. A., Boppart, M. D., Kavazis, A. N., Reidy, P. T., Ogasawara, R., et al. (2023) · Physiological Reviews · doi:10.1152/physrev.00039.2022 · Cited by 214 · see citing works
Myokines 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 · see citing works
Exercise therapy for people with sarcopenic obesity: myokines and adipokines as effective actors
Alizadeh Pahlavani, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.811751 · Cited by 145 · see citing works
Weng, K., Huo, W., Li, Y., Zhang, Y., Zhang, Y., Chen, G., & Xu, Q. (2021) · Poultry Science · doi:10.1016/j.psj.2021.101537 · Cited by 133 · see citing works
Turner, D. C., Seaborne, R. A. E., & Sharples, A. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-40787-0 · Cited by 132 · see citing works
Boyer, J. G., Prasad, V., Song, T., Lee, D., Fu, X., Grimes, K. M., Sargent, M. A., Sadayappan, S., & Molkentin, J. D. (2019) · JCI Insight · doi:10.1172/jci.insight.127356 · Cited by 75 · see citing works
The skeletal muscle fiber: a mechanically sensitive cell
Olsen, L. A., Nicoll, J. X., & Fry, A. C. (2019) · European Journal of Applied Physiology · doi:10.1007/s00421-018-04061-x · Cited by 73 · see citing works
Childs, C. J., Poling, H. M., Chen, K., Tsai, Y.-H., Wu, A., Vallie, A., Eiken, M. K., Huang, S., Sweet, C. W., Schreiner, R. P., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.02.007 · Cited by 72 · see citing works
Remiszewski, P., Jarocka-Karpowicz, I., Biernacki, M., Jastrząb, A., Schlicker, E., Toczek, M., Harasim‐Symbor, E., Pędzińska‐Betiuk, A., & Malinowska, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041295 · Cited by 60 · see citing works
Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise
MacDonald, T. L., Pattamaprapanont, P., Pathak, P., Fernandez, N., de Freitas, E. C., Hafida, S., Mitri, J., Britton, S. L., Koch, L. G., & Lessard, S. J. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0240-7 · Cited by 56 · see citing works
Self-citationMyopalladin promotes muscle growth through modulation of the serum response factor pathway
Filomena, M. C., Yamamoto, D. L., Caremani, M., Kadarla, V. K., Mastrototaro, G., Serio, S., Vydyanath, A., Mutarelli, M., Garofalo, A., Pertici, I., et al. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12486 · Cited by 50 · see citing works
Mulder, S. E., Dasgupta, A., King, R. J., Abrego, J., Attri, K. S., Murthy, D., Shukla, S. K., & Singh, P. K. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.07.025 · Cited by 47 · see citing works
Cellular and molecular pathways controlling muscle size in response to exercise
Attwaters, M., & Hughes, S. M. (2021) · FEBS Journal · doi:10.1111/febs.15820 · Cited by 45 · see citing works
Physical exercise: An inducer of positive oxidative stress in skeletal muscle aging
Thirupathi, A., Pinho, R. A., & Chang, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117630 · Cited by 39 · see citing works
Sodium-glucose co-transporter 2 inhibitors and Sarcopenia: A controversy that must be solved
Afşar, B., & Afşar, R. E. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.10.004 · Cited by 38 · see citing works
Energy metabolism and frailty: The potential role of exercise-induced myokines – A narrative review
Barros, D. G. M., Marques, E. A., Magalhães, J., & Carvalho, J. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101780 · Cited by 36 · see citing works
Microenvironmental innate immune signaling and cell mechanical responses promote tumor growth
Zhou, J., Valentini, E., & Boutros, M. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.06.007 · Cited by 35 · see citing works
Systemic Blockade of ACVR2B Ligands Protects Myocardium from Acute Ischemia-Reperfusion Injury
Magga, J. M., Vainio, L., Kilpiö, T., Hulmi, J. J., Taponen, S., Lin, R., Ramste, M. O., Szabó, Z., Gao, E., Rahtu‐Korpela, L., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.013 · Cited by 34 · see citing works
The ties that bind: functional clusters in limb-girdle muscular dystrophy
Barton, E. R., Pacak, C. A., Stoppel, W. L., & Kang, P. B. (2020) · Skeletal Muscle · doi:10.1186/s13395-020-00240-7 · Cited by 35 · see citing works
Nordgaard, C., Vind, A., Stonadge, A., Kjøbsted, R., Snieckute, G., Antas, P., Blasius, M., Reinert, M. S., Martínez‐Val, A., Bekker‐Jensen, D. B., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022111650 · Cited by 34 · see citing works
Ahsan, M., Garneau, L., & Aguer, C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1040809 · Cited by 30 · see citing works
HER2-driven breast cancer suppression by the JNK signaling pathway
Itah, Z., Chaudhry, S., Ponny, S. R., Aydemir, Ö., Lee, A., Cavanagh, J., Tournier, C., Muller, W. J., & Davis, R. J. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2218373120 · Cited by 28 · see citing works
Self-citationEpigenetic and "redoxogenetic" adaptation to physical exercise.
Radák, Z., Pan, L., Zhou, L., Mozaffaritabar, S., Gu, Y.-D., Pinho, R. A., Zheng, X., Ba, X.-Q., & Boldogh, I. (2023) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2023.11.005 · Cited by 26 · see citing works
Kusić, D., Connolly, J., Kainulainen, H., Semenova, E. A., Borisov, O., Larin, A. K., Викторович, П. Д., Generozov, E. V., Ahmetov, I. I., Britton, S. L., et al. (2019) · Physiological Genomics · doi:10.1152/physiolgenomics.00103.2019 · Cited by 24 · see citing works
McIntosh, M. C., Sexton, C. L., Godwin, J. S., Ruple, B. A., Michel, J. M., Plotkin, D. L., Ziegenfuss, T. N., Lopez, H. L., Smith, R. C., Dwaraka, V. B., et al. (2023) · Cells · doi:10.3390/cells12060898 · Cited by 25 · see citing works
Willoughby, D. S., Cardaci, T. D., Machek, S. B., Wilburn, D. T., & Heileson, J. L. (2022) · Journal of Sports Science and Medicine · doi:10.52082/jssm.2022.616 · Cited by 24 · see citing works
Cdon mutation and fetal alcohol converge on Nodal signaling in a mouse model of holoprosencephaly
Hong, M., Christ, A., Christa, A., Willnow, T. E., & Krauss, R. S. (2020) · eLife · doi:10.7554/elife.60351 · Cited by 23 · see citing works
MacDonald, T. L., Pattamaprapanont, P., Cooney, E. M., Nava, R. C., Mitri, J., Hafida, S., & Lessard, S. J. (2022) · Diabetes · doi:10.2337/db21-0934 · Cited by 20 · see citing works
Self-citationTan, Z., Zhao, M., Li, J., Li, S., Zhu, S., Yao, X., Gao, X., & Yang, S. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-377 · Cited by 19 · see citing works
Zhang, X., Sun, W., He, L., Wang, L., Qiu, K., & Yin, J. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02053-3 · Cited by 19 · see citing works
Moberg, M., Apró, W., Horwath, O., van Hall, G., Blackwood, S. J., & Katz, A. (2022) · Acta Physiologica · doi:10.1111/apha.13771 · Cited by 18 · see citing works
Nicoll, J. X., Fry, A. C., Mosier, E. M., Olsen, L. A., & Sontag, S. A. (2019) · European Journal of Applied Physiology · doi:10.1007/s00421-019-04200-y · Cited by 18 · see citing works
Signaling networks governing skeletal muscle growth, atrophy, and cachexia
Joshi, A. S., da Silva, M. T., Kumar, S., & Kumar, A. (2025) · Skeletal Muscle · doi:10.1186/s13395-025-00397-z · Cited by 20 · see citing works
Shi, Y., Zhou, D., Wang, H., Huang, L., Gao, X., Maitiabula, G., Zhang, L., & Wang, X. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13670 · Cited by 17 · see citing works
Nissinen, T. A., Hentilä, J., Fachada, V., Lautaoja-Kivipelto, J. H., Pasternack, A. H., Ritvos, O., Kivelä, R., & Hulmi, J. J. (2021) · The FASEB Journal · doi:10.1096/fj.202002008r · Cited by 17 · see citing works
PEG35 as a Preconditioning Agent against Hypoxia/Reoxygenation Injury
Silva, R., Machado, I. F., Teodoro, J. S., Rosello, A. P., Roselló‐Catafau, J., Rolo, A. P., & Palmeira, C. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031156 · Cited by 17 · see citing works
Zhao, Y., Xia, X., Wang, Q., Hu, D., Zhang, L., Li, X., Ding, X., Guo, H., & Guo, Y. (2022) · Cells · doi:10.3390/cells12010059 · Cited by 16 · see citing works
Voluntary Resistance Running as a Model to Induce mTOR Activation in Mouse Skeletal Muscle
D’Hulst, G., Palmer, A. S., Masschelein, E., Bar‐Nur, O., & Bock, K. D. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01271 · Cited by 16 · see citing works
DUX4 expression activates JNK and p38 MAP kinases in myoblasts
Brennan, C. M., Hill, A. S., Andre, M. S., Li, X., Madeti, V., Breitkopf, S. B., Garren, S. B., Xue, L., Gilbert, T. J., Hadjipanayis, A. G., et al. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049516 · Cited by 15 · see citing works
Mechanotransduction for Muscle Protein Synthesis via Mechanically Activated Ion Channels
Mirzoev, T. M. (2023) · Life · doi:10.3390/life13020341 · Cited by 14 · see citing works
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 14 · see citing works
Hansson, B., Olsen, L. A., Nicoll, J. X., von Walden, F., Melin, M., Strömberg, A., Rullman, E., Gustafsson, T. P., Fry, A. C., Fernandez‐Gonzalo, R., et al. (2019) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00022.2019 · Cited by 13 · see citing works
Zavvarian, M.-M., Hong, J., Khazaei, M., Chio, J. C. T., Wang, J., Badner, A., & Fehlings, M. G. (2021) · Biomolecules · doi:10.3390/biom11070972 · Cited by 13 · see citing works
Lautaoja-Kivipelto, J. H., O’Connell, T. M., Mäntyselkä, S., Peräkylä, J., Kainulainen, H., Pekkala, S., Permi, P., & Hulmi, J. J. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00133.2021 · Cited by 12 · see citing works
Teodoro, J. S., Machado, I. F., Castela, A. C., Amorim, J. A., Jarak, I., Carvalho, R. A., Palmeira, C. M., & Rolo, A. P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111738 · Cited by 12 · see citing works
Fowler, A., Knaus, K. R., Khuu, S., Khalilimeybodi, A., Schenk, S., Ward, S. R., Fry, A. C., Rangamani, P., & McCulloch, A. D. (2024) · Experimental Physiology · doi:10.1113/ep091712 · Cited by 9 · see citing works
CCL2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor models
Alissa, N., Fang, W. B., Medrano, M., Bergeron, N., Kozai, Y., Hu, Q., Redding, C., Thyfault, J. P., Hamilton‐Reeves, J. M., Berkland, C. J., et al. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050398 · Cited by 11 · see citing works
Feng, L., Li, B., Yong, S. S., & Tian, Z. (2024) · Journal of Science in Sport and Exercise · doi:10.1007/s42978-024-00295-8 · Cited by 11 · see citing works
Mendes, S., Leal, D. V., Baker, L. A., Ferreira, A., Smith, A. C., & Viana, J. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076017 · Cited by 12 · see citing works
MAPK family genes' influences on myogenesis in cattle: Genome-wide analysis and identification
Li, B., Wang, J., Raza, S. H. A., Wang, S., Liang, C., Zhang, W., Yu, S., Shah, M. A., Abdulmonem, W. A., Alharbi, Y. M., et al. (2023) · Research in Veterinary Science · doi:10.1016/j.rvsc.2023.04.024 · Cited by 11 · see citing works
O’Leary, M. F., Jackman, S. R., & Bowtell, J. L. (2024) · European Journal of Nutrition · doi:10.1007/s00394-023-03310-w · Cited by 11 · see citing works
Tan, Q., He, Q., Peng, Z., Zeng, X., Liu, Y., Li, D., Wang, S., & Wang, J. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02041-z · Cited by 11 · see citing works
The Effect of Mechanical Stretch on Myotube Growth Suppression by Colon-26 Tumor-Derived Factors
Halle, J. L., Counts, B. R., Prince, R. M., & Carson, J. A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.690452 · Cited by 11 · see citing works
β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?
Vived, C., Lee-Papastavros, A., Pereira, J. A. D. S., Peng, Y., & MacDonald, T. L. (2023) · Endocrinology · doi:10.1210/endocr/bqad162 · Cited by 9 · see citing works
Self-citationBeyond protein synthesis: non-translational functions of threonyl-tRNA synthetases
Barai, P., & Chen, J. (2024) · Biochemical Society Transactions · doi:10.1042/bst20230506 · Cited by 9 · see citing works
DNA repair byproduct 8-oxoguanine base promotes myoblast differentiation
Zheng, X., Zhang, W., Hu, Y., Zhao, Z., Wu, J., Zhang, X., Hao, F., Han, J., Xu, J. B., Hao, W., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102634 · Cited by 10 · see citing works
A Review on the Genetic Regulation of Myogenesis and Muscle Development
Liu, W. (2019) · American journal of biochemistry & biotechnology/American journal of biochemistry and biotechnology · doi:10.3844/ajbbsp.2019.1.12 · Cited by 9 · see citing works
Type 2 diabetes-related sarcopenia: role of nitric oxide
Bahadoran, Z., Mirmiran, P., & Ghasemi, A. (2024) · Nutrition & Metabolism · doi:10.1186/s12986-024-00883-z · Cited by 8 · see citing works
Machek, S. B., Cardaci, T. D., & Willoughby, D. S. (2020) · Strength and conditioning journal · doi:10.1519/ssc.0000000000000556 · Cited by 8 · see citing works
Dai, C., Reyes‐Ordoñez, A., You, J., & Chen, J. (2021) · The FASEB Journal · doi:10.1096/fj.202101094r · Cited by 8 · see citing works
Guzzoni, V., Shrestha, U., Kesler, N. J., Acharya, A., McKee, S. J., Cunha, T. S., Casarini, D. E., Haller, S. T., Kennedy, D. J., Britton, S. L., et al. (2025) · Comprehensive physiology · doi:10.1002/cph4.70029 · Cited by 6 · see citing works
Mowry, K. C., Thomson, T., Morales, C., Fikes, K. K., Stutts, K. J., Leatherwood, J. L., Anderson, M. J., Smith, R. X., & Suagee-Bedore, J. K. (2022) · Animals · doi:10.3390/ani12213006 · Cited by 7 · see citing works
West, D. W. D., Doering, T. M., Thompson, J. M., Budiono, B. P., Lessard, S. J., Koch, L. G., Britton, S. L., Steck, R., Byrne, N. M., Brown, M. A., et al. (2021) · Experimental Physiology · doi:10.1113/ep089301 · Cited by 7 · see citing works
Self-citationSamali, S. A., Hosseini, S. F., Mohammadi, Y., Sadri, F., & Rezaei, Z. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-11390-6 · Cited by 6 · see citing works
Sadri, S., Sharifi, G., & Dehkordi, K. J. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117641 · Cited by 6 · see citing works
Low Response to Aerobic Training in Metabolic Disease: Role of Skeletal Muscle
Soares, R. N., & Lessard, S. J. (2023) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000331 · Cited by 6 · see citing works
Self-citationRegulation of Hepatic Follistatin Expression at Rest and during Exercise in Mice
Peppler, W. T., Castellani, L. N., Root-McCaig, J., Townsend, L. K., SUTTON, C. D., Frendo‐Cumbo, S., Medak, K. D., MacPherson, R. E. K., Charron, M. J., & Wright, D. C. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001893 · Cited by 6 · see citing works
Eftestøl, E., Franchi, M. V., Kasper, S., & Flück, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-94930-x · Cited by 7 · see citing works
Pigg, Q. W., Harris, D. R., Inoue, D. S., & Gomes, M. J. (2025) · Antioxidants · doi:10.3390/antiox14070870 · Cited by 5 · see citing works
Effect of cigarette smoke extract on mitochondrial division in mouse quadriceps femoris cells
Tan, Z., Li, S., Zhu, S., Yao, X., Li, J., Gao, X., & Yang, S. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-5891 · Cited by 5 · see citing works
Yang, H., Zhang, C., Kim, W., Shi, M., Kılıçlıoğlu, M., Bayram, C., Bolat, İ., Tozlu, Ö. Ö., Baba, C., Yuksel, N., et al. (2024) · eLife · doi:10.7554/elife.98427 · Cited by 5 · see citing works
Dorry, S., Perla, S., & Bennett, A. M. (2024) · Molecular and Cellular Biology · doi:10.1080/10985549.2024.2426665 · Cited by 4 · see citing works
ExermiR‐129‐3p Enhances Muscle Function by Improving Mitochondrial Activity Through PARP1 Inhibition
Shin, Y. J., Yang, J. W., Jeong, H., Kim, J., Lee, B., Kim, J., Lee, S. M., Kwak, J. Y., Son, Y. H., Kim, K. J., et al. (2025) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13823 · Cited by 4 · see citing works
Nicoll, J. X., Fry, A. C., & Mosier, E. M. (2022) · European Journal of Applied Physiology · doi:10.1007/s00421-022-05085-0 · Cited by 4 · see citing works
Lee, C. J., & Nicoll, J. X. (2023) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000004409 · Cited by 4 · see citing works
Zhang, Y., & Qiu, Y. (2026) · Sports · doi:10.3390/sports14050212 · Cited by 3 · see citing works
“Mechanistic insights from cell and animal studies suggest that when muscle is subjected to mechanical stress, it can downregulate MSTN expression via pathways such as JNK-mediated phosphorylation of transcription factor Smad2 [55,57].”
Gupta, A., Hadj‐Moussa, H., Al-attar, R., Seibel, B. A., & Storey, K. B. (2021) · Physiological and Biochemical Zoology · doi:10.1086/714097 · Cited by 3 · see citing works
Hermann, H. J., Wuebbles, R. D., Dagda, M., Muñoz, A., Parker, L. L., Guzman, P. C. C., Byrne, L. T., Moore, S. A., & Burkin, D. J. (2025) · JCI Insight · doi:10.1172/jci.insight.194581 · Cited by 2 · see citing works
Tension to Translation: External to Internal Processes in Muscle Hypertrophy
Greyvenstein, D., Newbold, J. P., & Phillips, S. M. (2025) · Physiology · doi:10.1152/physiol.00034.2025 · Cited by 3 · see citing works
Advancing cancer cachexia diagnosis with -omics technology and exercise as molecular medicine
Hesketh, S. J. (2024) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2024.01.006 · Cited by 2 · see citing works
Underlying mechanisms of sarcopenic obesity
Rauen, M., Bollheimer, L. C., & Nourbakhsh, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00005-3 · Cited by 2 · see citing works
MAPK Phosphatase-5 is required for TGF-β signaling through a JNK-dependent pathwayPreprint
Dorry, S., Perla, S., & Bennett, A. M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.27.600976 · Cited by 2 · see citing works
Lu, J., Yu, L., & Shi, J. (2022) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.20210777 · Cited by 1 · see citing works
Biological Roles of MAP Kinases
De, S. K. (2024) · Springer eBooks · doi:10.1007/978-3-031-75682-5_2 · Cited by 1 · see citing works
Yang, H., Zhang, C., Kim, W., Shi, M., Kılıçlıoğlu, M., Bayram, C., Bolar, I., Tozlu, Ö. Ö., Baba, C., Yuksel, N., et al. (2025) · eLife · doi:10.7554/elife.98427.3 · Cited by 1 · see citing works
Semnan, F. M., Anbaran, M. B., Bayati, M., Amani-Shalamzari, S., & Carneiro, L. S. R. D. S. F. (2026) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2026.1761170 · Cited by 1 · see citing works
Sanfrancesco, V. C., Mea, D. D., & Hood, D. A. (2026) · Muscles · doi:10.3390/muscles5020039 · Cited by 1 · see citing works
Sarcopenia: Technological Advances in Measurement and Rehabilitation
Lorusso, L., Esposito, L., Sancarlo, D., & D’Onofrio, G. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.101278 · Cited by 1 · see citing works
Short‐term disuse shapes the adaptive response to resistance training
Andresen, J. (2025) · The Journal of Physiology · doi:10.1113/jp288530 · Cited by 1 · see citing works
Cdon mutation and fetal alcohol converge on Nodal signaling in a mouse model of holoprosencephalyPreprint
Hong, M., Christ, A., Christa, A., Willnow, T. E., & Krauss, R. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.30.070870
Zheng, X., Zhang, W., Wu, J., Hu, Y., Zhang, X., Hao, F., Han, J., Hao, W., Wang, R., Tian, M., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1473019/v1
Phillips, S. M. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735320205.793571145
Faculty Opinions recommendation of JNK regulates muscle remodeling via myostatin/SMAD inhibition.
Debold, E. P. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733755069.793550548
Yang, H., Zhang, C., Kim, W., Shi, M., Kılıçlıoğlu, M., Bayram, C., Bolat, İ., Tozlu, Ö. Ö., Baba, C., Yuksel, N., et al. (2024) · eLife · doi:10.7554/elife.98427.1
Yang, H., Zhang, C., Kim, W., Shi, M., Kılıçlıoğlu, M., Bayram, C., Bolat, İ., Tozlu, Ö. Ö., Baba, C., Yuksel, N., et al. (2025) · eLife · doi:10.7554/elife.98427.2
- Authors
- Lessard, S. J., MacDonald, T. L., Pathak, P., Han, M. S., Coffey, V. G., Edge, J., Rivas, D. A., Hirshman, M. F., Davis, R. J., & Goodyear, L. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Joslin Diabetes Center (US)
- University of Massachusetts Chan Medical School (US)
- Bond University (AU)
- Massey University (NZ)
- Tufts University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lessard, Sarah J.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-08-02
- Volume
- 9
- Issue
- 1
- Pages
- 3030-3030
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6072737
- OpenAlex
- W2884155806
- Cited by
- 119
- References
- 57
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 16 · 2023: 14 · 2022: 17 · 2021: 14 · 2020: 21 · 2019: 12 · 2018: 1
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion, cc-by)
- Bond University Research Portal (Bond University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- American Heart Association (15SDG25560057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- c-Jun N-terminal kinase, skeletal muscle remodeling, myostatin, Smad2, resistance training, endurance exercise, muscle fiber growth, muscle oxidative capacity, cardiorespiratory fitness, mechanical stress, Smad2 phosphorylation, muscle mass
- MeSH terms
- Adult, Animals, Cell Nucleus, Enzyme Activation, Gene Expression Regulation, Humans, Hypertrophy, Mice, Inbred C57BL, Muscles, Phosphorylation, Physical Conditioning, Animal, Physical Endurance, Signal Transduction, Mice, Knockout, Muscle, Skeletal, Integrases, Protein Transport, Muscle Development, JNK Mitogen-Activated Protein Kinases, Smad Proteins, Myostatin, HEK293 Cells
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