TNF-α is a mitogen in skeletal muscle
Abstract
Emerging evidence suggests that tumor necrosis factor (TNF)-alpha plays a role in muscle repair. To determine whether TNF-alpha modulates satellite cell proliferation, the current study evaluated TNF-alpha effects on DNA synthesis in primary myoblasts and on satellite cell activation in adult mouse muscle. Exposure to recombinant TNF-alpha increased total DNA content in rat primary myoblasts dose-dependently over a 24-h period and increased the number of primary myoblasts incorporating 5-bromo-2'-deoxyuridine (BrdU) during a 30-min pulse labeling. Systemic injection of TNF-alpha stimulated BrdU incorporation by satellite cells in muscles of adult mice, whereas no BrdU was incorporated by satellite cells in control mice. TNF-alpha stimulated serum response factor (SRF) binding to the serum response element (SRE) present in the c-fos gene promoter and stimulated reporter gene expression controlled by the same element. Our data suggest that TNF-alpha activates satellite cells to enter the cell cycle and accelerates G1-to-S phase transition, and these actions may involve activation of early response genes via SRF.
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TNF-α acts as a mitogen for satellite cells.
“Other data support the anabolic effects of TNF-α, which acts as a mitogen for satellite cells [38].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [38]
Initially infiltrating M1 macrophages produce chemokines and cytokines (TNF-α, IL-1β, IL-6) that are chemoattractant and mitogenic for muscle progenitor cells, including Pax7+ satellite cells.
“Briefly, a number of studies have shown that the chemokines and cytokines (TNF-α, IL-1β, IL-6) produced by initially infiltrating M1 macrophages are chemoattractant and mitogenic for muscle progenitor cells, including Pax7+ satellite cells [115–119].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [119]
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- Authors
- Li, Y.-P.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Li, Yi-Ping
- ORCID
- Li, Yi-Ping
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2003-08
- Volume
- 285
- Issue
- 2
- Pages
- C370-C376
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W1972955532
- Cited by
- 249
- References
- 56
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 15 · 2020: 13 · 2019: 13 · 2018: 11 · 2017: 13 · 2016: 11 · 2015: 14 · 2014: 17 · 2013: 11 · 2012: 12
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL59878, R01HL059878)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- TNF-α, satellite cells, skeletal muscle, muscle repair, myoblast proliferation, DNA synthesis, cell cycle, G1/S transition, serum response factor, serum response element, c-fos promoter, early response genes, mitogens
- MeSH terms
- Animals, Animals, Newborn, Cell Division, Cells, Cultured, DNA, Dose-Response Relationship, Drug, Male, Mice, Inbred ICR, Promoter Regions, Genetic, Regeneration, Tumor Necrosis Factor-alpha, Proto-Oncogene Proteins c-fos, Genes, Reporter, Muscle, Skeletal, Serum Response Factor, Serum Response Element, Myoblasts, Satellite Cells, Skeletal Muscle, Mice, Rats
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