TNF-alpha is a mitogen in skeletal muscle.
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.
Li
Yi-Ping
YP
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Suite 520B, Houston, TX 77030, USA. yiping@bcm.tmc.edu
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics; D051381:Rats; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000378:metabolism*; D027602:Serum Response Element / Q000187:drug effects / Q000235:genetics; D026362:Serum Response Factor / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D014409:Tumor Necrosis Factor-alpha; D004247:DNA