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
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Self-citationCapric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis
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Peake, J., Neubauer, O., Gatta, P. D. D., & Nosaka, K. (2016) · Journal of applied physiology · doi:10.1152/japplphysiol.00971.2016 · Cited by 740
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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
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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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