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IL-7 is expressed and secreted by human skeletal muscle cells
Abstract
In addition to generating movement, skeletal muscle may have a function as a secretory organ. The aim of the present study was to identify novel proteins with signaling capabilities secreted from skeletal muscle cells. IL-7 was detected in media conditioned by primary cultures of human myotubes differentiated from satellite cells, and concentrations increased with incubation time. By immunoblotting and real-time RT-PCR IL-7 expression was confirmed at both protein and mRNA levels. Furthermore, with immunofluorescence and specific antisera, multinucleated myotubes were found to coexpress IL-7 and myosin heavy chain. During differentiation of human myotubes from satellite cells, IL-7 expression increased at mRNA and protein levels. In contrast, mRNA expression of the IL-7 receptor was 80% lower in myotubes compared with satellite cells. Incubations with recombinant IL-7 under differentiation conditions caused approximately 35% reduction in mRNA for the terminal myogenic markers myosin heavy chain 2 (MYH2) and myogenin (MYOG), suggesting that IL-7 may act on satellite cells to inhibit development of the muscle fiber phenotype. Alternative routes of cell development were investigated, and IL-7 increased migration of satellite cells by 40% after 48 h in a Transwell system, whereas cell proliferation remained unchanged. In vivo, real-time RT-PCR analysis of musculus vastus lateralis (n = 10) and musculus trapezius (n = 7) biopsies taken from male individuals undergoing a strength training program demonstrated that after 11 wk mean IL-7 mRNA increased by threefold (P = 0.01) and fourfold (P = 0.04), respectively. In conclusion, we have demonstrated that IL-7 is a novel myokine regulated both in vitro and in vivo, and it may play a role in the regulation of muscle cell development.
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“A number of other myokines, including IL‑15 (53) and IL-7 (54) have further been demonstrated to possess anabolic features in rodent models.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [54]
In the citing paper
“A post-exercise surge in thymopoiesis is possible considering that skeletal muscle secretes IL-7 (Haugen et al. 2010) which might in turn increase thymic mass and lead to the emergence of recent thymic emigrants (Fry and Mackall 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Haugen et al. 2010
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Myonectin deletion promotes adipose fat storage and reduces liver steatosis
Little, H. C., Rodriguez, S., Lei, X., Tan, S. Y., Stewart, A. N., Sahagun, A., Sarver, D. C., & William Wong, G. (2019) · The FASEB Journal · doi:10.1096/fj.201900520r · Cited by 78
“Of the hundreds of proteins secreted by skeletal muscle (7–9), only a few have been functionally characterized, includingmyostatin (10–12), IL-6 (13), fibroblast growth factor 21 (14, 15), insulin-like 6 (16), follistatinlike 1 (17), leukemia inhibitory factor (18), IL-7 (19), IL-15 (20), musclin (21, 22), and irisin…”
BackgroundPhysical Exercise as a Multimodal Tool for COVID-19: Could It Be Used as a Preventive Strategy?
Fernández‐Lázaro, D., González-Bernal, J. J., Sánchez-Serrano, N., Navascués, L. J., Ascaso-del-Rio, A., & Mielgo‐Ayuso, J. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17228496 · Cited by 83
“In this sense, by immunoblotting and real-time reverse transcription polymerase chain reaction (RT-PCR), the IL-7 expression was confirmed with both protein and mRNA increased levels by regular moderate Ex [50], which could stimulate thymus function when IL-7 increases in plasma.”
BackgroundMicrophysiological Analysis Platform of Pancreatic Islet β‐Cell Spheroids
Lee, S. H., Hong, S., Song, J., Cho, B., Han, E. J., Kondapavulur, S., Kim, D., & Lee, L. P. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201701111 · Cited by 78
Gu, S., Zhao, L., Wu, Y., Li, S., Sun, J., Huang, J., & Li, D. (2015) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-015-1838-x · Cited by 74
Differential Bone Loss in Mouse Models of Colon Cancer Cachexia
Bonetto, A., Kays, J. K., Parker, V. A., Matthews, R. R., Barreto, R., Puppa, M., Kang, K. S., Carson, J. A., Guise, T. A., Mohammad, K. S., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2016.00679 · Cited by 73
“…cytokines, such as IL-6, IL7, and IL-15, were originally described in association with muscle contraction and exercise, thus further supporting the idea that mechanical stimulation is fundamental to maintain bone integrity (Nielsen et al., 2007; Pedersen, 2009; Haugen et al., 2010; Hamrick, 2012).”
BackgroundMuscle cell‐derived cytokines in skeletal muscle regeneration
Waldemer, R. J., Kim, D., & Chen, J. (2022) · FEBS Journal · doi:10.1111/febs.16372 · Cited by 79
Regulation of tissue crosstalk by skeletal muscle-derived myonectin and other myokines
Seldin, M. M., & Wong, G. W. (2012) · Adipocyte · doi:10.4161/adip.20877 · Cited by 69
Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis
Chan, C. Y. X., Masui, O., Krakovska, O., Belozerov, V. E., Voisin, S. N., Ghanny, S., Chen, J., Dharsee, M., Zhu, P., Evans, K., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.004804 · Cited by 69
“Apart from the well-known myokines, such as members of the insulin-like growth factor-1 (54–63) and transforming growth factor (TGF) families (64– 72), there are studies investigating other myokines, such as plasminogen activator (73), collagenase (74), decorin (75), glial growth factor (76), neurocrescin (77), meltri…”
BackgroundKim, M. H., Kay, D. I., Rudra, R. T., Chen, B. M., Hsu, N., Izumiya, Y., Martinez, L., Spencer, M. J., Walsh, K. X., Grinnell, A. D., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr015 · Cited by 67
“It is feasible that myokine production downstream of Akt indirectly promotes satellite cell differentiation through paracrine signaling from mature myofibers (64) and autocrine amplification of IGF-1 receptor stimulation from differentiating myoblasts (61).”
BackgroundTurner, J. E., & Brum, P. C. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4234765 · Cited by 66
“Finally, contracting skeletal muscle secretes IL-7 [67] which might increase thymic mass and promote the emergence of recent thymic emigrants [68].”
BackgroundHjorth, M., Norheim, F., Meen, A. J., Pourteymour, S., Lee-Ødegård, S., Holen, T., Jensen, J., Birkeland, K. I., Martinov, V. N., Langleite, T. M., et al. (2015) · Physiological Reports · doi:10.14814/phy2.12473 · Cited by 73
“vastus lateralis of five healthy, male donors (33–53 years of age) were isolated as previously described (Haugen et al. 2010).”
MethodPerilipin 4 in human skeletal muscle: localization and effect of physical activity
Pourteymour, S., Lee-Ødegård, S., Langleite, T. M., Eckardt, K., Hjorth, M., Bindesbøll, C., Dalen, K. T., Birkeland, K. I., Drevon, C. A., Holen, T., et al. (2015) · Physiological Reports · doi:10.14814/phy2.12481 · Cited by 62
“3 software (Applied Biosystems) as previously described (Haugen et al. 2010).”
MethodInfluentialWeigert, C., Lehmann, R., Hartwig, S., & Lehr, S. (2013) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201300094 · Cited by 61
The Importance of Biophysical and Biochemical Stimuli in Dynamic Skeletal Muscle Models
Maleiner, B., Tomasch, J., Heher, P., Oliver Spadiut, A., Rünzler, D., & Fuchs, C. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01130 · Cited by 60
Ringleb, M., Javelle, F., Haunhorst, S., Bloch, W., Fennen, L., Baumgart, S., Drube, S., Reuken, P. A., Pletz, M. W., Wagner, H., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202301619r · Cited by 73
“Literature was searched to examine the acute changes in circulating levels of immunoregulatory myokines (i.e., IL-6, IL-10, IL-1ra, TNF-α , IL-15, IL-7, TGF-β 1, and FKN) induced by a bout of resistance exercise.”
BackgroundInfluentialMyokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance
Yi, J., Chen, J., Yao, X., Zhao, Z., Niu, X., Li, X., Sun, J., Ji, Y., Shang, T., Gong, L., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117326 · Cited by 68
Regulation of angiopoietin-like protein 4 production during and after exercise
Norheim, F., Hjorth, M., Langleite, T. M., Lee, S., Holen, T., Bindesbøll, C., Stadheim, H. K., Gulseth, H. L., Birkeland, K. I., Kielland, A., et al. (2014) · Physiological Reports · doi:10.14814/phy2.12109 · Cited by 53
“Using High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA), 1000 ng of total RNA from human and mouse tissue samples or cells was converted into cDNA.”
BackgroundMethodInfluentialHanssen, K. E., Kvamme, N. H., Nilsen, T. S., Rønnestad, B. R., Ambjørnsen, I. K., Norheim, F., Kadi, F., Hallén, J., Drevon, C. A., & Raastad, T. (2012) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.2012.01452.x · Cited by 53
“Other analyses of growth factors and myostatin in 10 selected subjects are as follows: Further analyses were either performed in 96-well plates (MGF) or with a custom-made 384-well microfluid card containing 96 predeveloped assays (Haugen et al., 2010).”
MethodBone-muscle crosstalk under physiological and pathological conditions
Dong, Y., Yuan, H., Ma, G., & Cao, H. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05331-y · Cited by 52
“IL7 signal has the potential to sustain the phenotype of SCs, which is evident in its ability to facilitate cellular migration and the expression of PAX7 , a marker of SCs that prevents myogenesis [67].”
BackgroundRoca-Rivada, A., Al–Massadi, O., Castelao, C., Senín, L. L., Alonso, J., Seoane, L. M., García‐Caballero, T., Casanueva, F. F., & Pardo, M. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.06.037 · Cited by 50
Renin–angiotensin system in ureteric bud branching morphogenesis: insights into the mechanisms
Yosypiv, I. V. (2011) · Pediatric Nephrology · doi:10.1007/s00467-011-1820-2 · Cited by 46
Emery, A., Moore, S. E., Turner, J. E., & Campbell, J. P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.788113 · Cited by 49
“An important series of studies have shown that physically active individuals exhibit higher concentrations of immunoregulatory cytokines, such as interleukin (IL)-7 and IL-15 in blood (109, 127), which may be due to increased homeostatic cytokine output from skeletal muscle (102, 108) as both IL-15 and IL-7 are expres…”
BackgroundKoivisto, A., Olsén, T., Paur, I., Paulsen, G., Bastani, N. E., Garthe, I., Raastad, T., Matthews, J. B., Blomhoff, R., & Bøhn, S. K. (2019) · PLoS ONE · doi:10.1371/journal.pone.0217895 · Cited by 47
Skeletal Muscle Protein Tyrosine Phosphatase 1B Regulates Insulin Sensitivity in African Americans
Stull, A. J., Wang, Z. Q., Zhang, X. H., Yu, Y., Johnson, W. D., & Cefalu, W. T. (2012) · Diabetes · doi:10.2337/db11-0744 · Cited by 45
“RPLP0 gene encodes the human acidic ribosomal phosphoprotein large P0 subunit and is used as a special housekeeping gene for human skeletal muscle (31,32).”
BackgroundPathophysiological mechanism of acute bone loss after fracture
Zheng, X.-Q., Huang, J., Lin, J., & Song, C. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.08.019 · Cited by 47
Myokines and Microbiota: New Perspectives in the Endocrine Muscle–Gut Axis
Saponaro, F., Bertolini, A., Baragatti, R., Galfo, L., Chiellini, G., Saba, A., & D’Urso, G. (2024) · Nutrients · doi:10.3390/nu16234032 · Cited by 55
Zamboni, M. M., Mazzali, G., Brunelli, A., Saatchi, T., Urbani, S., Giani, A., Rossi, A. P., Zoico, E., & Fantin, F. (2022) · Cells · doi:10.3390/cells11213361 · Cited by 47
“Furthermore, IL-7 plays an essential role in myogenesis and may influence the differentiation of satellite cells into fully developed skeletal muscle cells [58].”
BackgroundCornish, S. M., Bugera, E. M., Duhamel, T. A., Peeler, J. D., & Anderson, J. E. (2020) · European Journal of Applied Physiology · doi:10.1007/s00421-020-04337-1 · Cited by 43
Shero, J. A., Lindholm, M. E., Sandri, M. F., & Stanford, K. I. (2025) · Circulation Research · doi:10.1161/circresaha.124.325614 · Cited by 45
Myokine Expression in Muscle and Myotubes in Response to Exercise Stimulation
Covington, J. D., Tam, C. S., Bajpeyi, S., Galgani, J. E., Noland, R. C., Smith, S. R., Redman, L. M., & Ravussin, É. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000787 · Cited by 38
“IL-15 and leukocyte-inducing factor (LIF) have been speculated to regulate muscle cell growth and satellite cell proliferation (7,18), with IL-15 playing a potential role in adipose tissue lipolysis (33).”
Xu, J., Tang, M., Wu, X., Kong, X., Liu, Y., & Xu, X. (2022) · Food & Function · doi:10.1039/d1fo03804d · Cited by 41
Cappellari, O., Mantuano, P., & Luca, A. D. (2020) · Cells · doi:10.3390/cells9071659 · Cited by 36
Renin–angiotensin system in ureteric bud branching morphogenesis: implications for kidney disease
Yosypiv, I. V. (2013) · Pediatric Nephrology · doi:10.1007/s00467-013-2616-3 · Cited by 34
Metadata
- Authors
- Haugen, F., Norheim, F., Lian, H., Wensaas, A. J., Dueland, S., Berg, O., Funderud, A., Skålhegg, B. S., Raastad, T., & Drevon, C. A.
- Affiliations
- University of Oslo (NO)
- Norwegian School of Sport Sciences (NO)
- Corresponding author
- Haugen, Fred
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2010-04
- Volume
- 298
- Issue
- 4
- Pages
- C807-C816
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2112164340
- Cited by
- 237
- References
- 50
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 24 · 2023: 14 · 2022: 14 · 2021: 17 · 2020: 20 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 18 · 2015: 18 · 2014: 8 · 2013: 15 · 2012: 18
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- IL-7, myokines, skeletal muscle, satellite cells, myotubes, myogenesis, IL-7 receptor, myosin heavy chain, myogenin, resistance training, vastus lateralis, trapezius, muscle fiber phenotype
- MeSH terms
- Adult, Cell Differentiation, Cells, Cultured, Culture Media, Humans, Male, Middle Aged, RNA, Messenger, Biomarkers, Interleukin-7, Muscle Fibers, Skeletal, Myosin Heavy Chains, Receptors, Interleukin-7, Muscle Development, Satellite Cells, Skeletal Muscle, Cell Proliferation, Resistance Training
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