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Cited by 162Muscle Physiology and DisordersCardiac Fibrosis and RemodelingWound Healing and Treatments

The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.

Role of TNF-α signaling in regeneration of cardiotoxin-injured muscle

Open access
Chen, Shuen-Ei, Gerken, Eric, Zhang, Yingmin, Zhan, Mei, Mohan, Raja K., Li, Andrew S., Reid, Michael B., Li, Yi-Ping·2005·American Journal of Physiology-Cell Physiology
DOI 10.1152/ajpcell.00062.2005PMC PMC3099530
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Abstract

Recent data suggest a physiological role for the proinflammatory cytokine TNF-alpha in skeletal muscle regeneration. However, the underlying mechanism is not understood. In the present study, we analyzed TNF-alpha-activated signaling pathways involved in myogenesis in soleus muscle injured by cardiotoxin (CTX) in TNF-alpha receptor double-knockout mice (p55(-/-)p75(-/-)). We found that activation of p38MAPK, which is critical for myogenesis, was blocked in CTX-injured p55(-/-)p75(-/-) soleus on day 3 postinjury when myogenic differentiation was being initiated, while activation of ERK1/2 and JNK MAPK, as well as transcription factor NF-kappaB, was not reduced. Consequently, the phosphorylation of transcription factor myocyte enhancer factor-2C, which is catalyzed by p38 and crucial for the expression of muscle-specific genes, was blunted. Meanwhile, expression of p38-dependent differentiation marker myogenin and p21 were suppressed. In addition, expression of cyclin D1 was fivefold that in wild-type (WT) soleus. These results suggest that myogenic differentiation is blocked or delayed in the absence of TNF-alpha signaling. Histological studies revealed abnormalities in regenerating p55(-/-)p75(-/-) soleus. On day 5 postinjury, new myofiber formation was clearly observed in WT soleus but not in p55(-/-)p75(-/-) soleus. To the contrary, p55(-/-)p75(-/-) soleus displayed renewed inflammation and dystrophic calcification. On day 12 postinjury, the muscle architecture of WT soleus was largely restored. Yet, in p55(-/-)p75(-/-) soleus, multifocal areas of inflammation, myofiber death, and myofibers with smaller cross-sectional area were observed. Functional studies demonstrated an attenuated recovery of contractile force in injured p55(-/-)p75(-/-) soleus. These data suggest that TNF-alpha signaling plays a critical regulatory role in muscle regeneration.

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Crossref · 10.1152/ajpcell.00062.2005

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  1. Storkus WJ, Tahara H, and Lotze MT. Interleukin-12. In: The Cytokine Handbook (3rd ed.), edited by Thomson AW. San Diego, CA: Academic, 1998, p. 391–426.

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Metadata

Authors
Chen, S.-E., Gerken, E., Zhang, Y., Zhan, M., Mohan, R. K., Li, A. S., Reid, M. B., & Li, Y.-P.
Affiliations
  • Baylor College of Medicine (US)
  • University of Kentucky (US)
ORCID
Venue
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Published
2005-11
Volume
289
Issue
5
Pages
C1179-C1187
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
DOI
10.1152/ajpcell.00062.2005
PMC
PMC3099530
OpenAlex
W2114596120
Cited by
162
References
50
Citations by year
2026: 3 · 2025: 4 · 2024: 9 · 2023: 9 · 2022: 6 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 10 · 2014: 15 · 2013: 5 · 2012: 11
FWCI
2.64
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL59878, R01HL059878)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049022, AR049022)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Surgery › Wound Healing and Treatments
Keywords
TNF signaling, skeletal muscle regeneration, cardiotoxin injury, p38 MAPK, myogenesis, myogenin, p21, cyclin D1, TNF receptor p55, TNF receptor 2, muscle inflammation, dystrophic calcification, soleus muscle
MeSH terms
Animals, Cobra Cardiotoxin Proteins, Enzyme Activation, Muscle Contraction, Muscular Diseases, Regeneration, Tumor Necrosis Factor-alpha, Signal Transduction, Receptors, Tumor Necrosis Factor, Mice, Knockout, Muscle, Skeletal, Muscle Development, p38 Mitogen-Activated Protein Kinases, Mice

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