The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
Interleukin-6/Signal Transducer and Activator of Transcription 3 (STAT3) Pathway Is Essential for Macrophage Infiltration and Myoblast Proliferation during Muscle Regeneration
Open accessAbstract
Inflammation and microenvironment play a crucial role in muscle regeneration. IL (interleukin)-6, as a multifunctional cytokine is involved in the processes. However, the causative effect of IL-6 in muscle regeneration remains unclear. In a mouse model of cardiotoxin-induced muscle injury/regeneration, infiltrated monocytes/macrophages produce a high level of IL-6 started on 1 day (24 h) after injury. In IL-6 knock-out (−/−) mice, the muscle regeneration procedure was impaired along with decreased myogenic determination factor (MyoD) and myogenin mRNA level and increased interstitial fibrosis. The IL-6 −/− mice exhibited less macrophage infiltration, lower inflammatory cytokine (IL-1β, inducible NO synthase, Transforming growth factor (TGF)-β1, and IL-10) and chemokine (CCL2, CCL3, and CCL5) expression, and inhibited myoblast proliferation. In vitro , IL-6 deficiency or Signal Transducer and Activator of Transcription 3 (STAT3) knockdown in activated macrophage attenuated the expression of CCL2, CCL3, but not CCL5, which resulted in less macrophage migration. Moreover, inflammatory macrophages promoted myoblast proliferation in an IL-6-dependent manner. Finally, adoptive transfer IL-6 +/+ BM cells into IL-6 −/− mice rescued the impaired regeneration with improved MyoD and myogenin expression. Taken together, IL-6 expression and the activated STAT3 signaling pathway in monocytes/macrophages is a critical mediator of macrophage migration and myoblast proliferation during muscle regeneration. Background: Interleukin-6 (IL-6), as a multifunctional cytokine, was involved in the inflammation microenvironment of muscle regeneration. Results: In mice lacking IL-6, less macrophage recruitment and decreased myoblast proliferation impairs muscle regeneration. Conclusion: In monocytes/macrophages, activation of the IL-6/STAT3 pathway is critical to macrophage migration and myoblast proliferation during muscle regeneration. Significance: IL-6/STAT3 pathway is essential for muscle regeneration.
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“Acute transient increases in inflammation plays an important part in the early regenerative processes of muscle adaptation, particularly in response to exercise [54,55].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [55]
Citations
Cites
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · cited 1×
“Necrotic cellular corps or damage-associated molecular patterns would activate the Toll like receptor (TLR) on the membranes of infiltrated monocytes/ macrophages, leading to inflammatory responses (24, 26, 27).”
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F. (2003) · Biochemical Journal · doi:10.1042/bj20030407 · Cited by 3,272 · cited 1×
“Once in the nucleus, p-STAT3 binds to the -interferon activation sequence element where it then promotes the transcription of downstream genes (32).”
Cellular and Molecular Regulation of Muscle Regeneration
CHARGÉ, S. B. P., & Rudnicki, M. A. (2004) · Physiological Reviews · doi:10.1152/physrev.00019.2003 · Cited by 2,691
Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002 · cited 5×
“When the monocyteswere depleted inWTmice, even if the proliferation capacity of myoblasts was similar, the regeneration was deficient (6, 7).”
InfluentialMyogenic satellite cells: physiology to molecular biology
Hawke, T. J., & Garry, D. J. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.2.534 · Cited by 1,646
Collins, C. A., Olsen, I., Zammit, P. S., Heslop, L., Petrie, A., Partridge, T. A., & Morgan, J. E. (2005) · Cell · doi:10.1016/j.cell.2005.05.010 · Cited by 1,445 · cited 1×
“The progression proceeds highly coordination by multiple factors (4, 5), including the endogenous signaling that controls SC self-activation, proliferation, and differentiation (2), and the interaction between SCs and microenvironment (i.”
Regulatory 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 · cited 2×
“How does IL-6 determine muscle regeneration? The process of muscle regeneration is complex, which includes not only the activation, proliferation, and differentiation of SCs, but also inflammatory cell infiltration, which promote SC proliferation and activation (1).”
Bours, M. J. L., Swennen, E. L. R., Di Virgilio, F., Cronstein, B. N., & Dagnelie, P. C. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.04.013 · Cited by 1,030
Interleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy
Serrano, A. L., Baeza-Raja, B., Perdiguero, E., Jardí, M., & Muñoz-Cánoves, P. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.011 · Cited by 873 · cited 1×
“reported that IL-6 can be produced by myoblasts and promoted myoblast proliferation and hypertrophy intrinsically (14); therefore, there is a possibility of that abnormal myoblasts in IL-6 / mice may also contribute to impaired muscle regeneration.”
Hurst, S. M., Wilkinson, T. S., McLoughlin, R. M., Jones, S., Horiuchi, S., Yamamoto, N., Rose-John, S., Fuller, G. M., Topley, N., & Jones, S. A. (2001) · Immunity · doi:10.1016/s1074-7613(01)00151-0 · Cited by 811 · cited 1×
“In acute inflammation, IL-6 could have a rather protective role by decreasing neutrophils and favoring monocyte recruitment through continuous CCL2 secretion (16).”
Cited by
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Interleukin‐6 myokine signaling in skeletal muscle: a double‐edged sword?
Muñoz‐Cánoves, P., Scheele, C., Pedersen, B. K., & Serrano, A. L. (2013) · The FEBS Journal · doi:10.1111/febs.12338 · Cited by 774
Muscle 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
Oishi, Y., & Manabe, I. (2018) · International Immunology · doi:10.1093/intimm/dxy054 · Cited by 770
AMPK in skeletal muscle function and metabolism
Kjøbsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M.-N., Pehmøller, C. K., Shum, M., Marette, A., Mounier, R., Treebak, J. T., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700442r · Cited by 517
Tailoring Materials for Modulation of Macrophage Fate
Li, J., Jiang, X., Li, H., Gelinsky, M., & Gu, Z. (2021) · Advanced Materials · doi:10.1002/adma.202004172 · Cited by 406
Metadata
- Authors
- Zhang, C., Li, Y., Wu, Y., Wang, L., Wang, X., & Du, J.
- Affiliations
- Capital Medical University (CN)
- Corresponding author
- Du, Jie
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 288
- Issue
- 3
- Pages
- 1489-1499
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3548462
- OpenAlex
- W1969630360
- Cited by
- 279
- References
- 37
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 21 · 2023: 17 · 2022: 20 · 2021: 23 · 2020: 21 · 2019: 20 · 2018: 27 · 2017: 25 · 2016: 22 · 2015: 19 · 2014: 20 · 2013: 12
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060268)
- 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 › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- interleukin-6, STAT3 signaling, muscle regeneration, macrophage infiltration, myoblast proliferation, cardiotoxin-induced muscle injury, IL-6 knockout mice, macrophage migration, MyoD, myogenin, interstitial fibrosis, inflammatory cytokines, bone marrow-derived macrophages
- MeSH terms
- Animals, Cell Movement, Gene Expression Regulation, Macrophages, Regeneration, RNA, Messenger, Signal Transduction, Interleukin-6, MyoD Protein, Myogenin, Mice, Knockout, Muscle, Skeletal, Myoblasts, Cell Proliferation, STAT3 Transcription Factor, Mice, Cardiotoxins, Primary Cell Culture
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