Tumor Necrosis Factor-Alpha Modulates Expression of Genes Involved in Cytokines and Chemokine Pathways in Proliferative Myoblast Cells

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 13; p. 1161
• Main Authors: Alvarez, Angela María, Trufen, Carlos Eduardo Madureira, Buri, Marcus Vinicius, de Sousa, Marcela Bego Nering, Arruda-Alves, Francisco Ivanio, Lichtenstein, Flavio, Castro de Oliveira, Ursula, Junqueira-de-Azevedo, Inácio de Loiola Meirelles, Teixeira, Catarina, Moreira, Vanessa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08-07-2024
• Subjects: Animals; Antibodies; Cell activation; Cell cycle; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Chemokines; Chemokines - genetics; Chemokines - metabolism; Collagenase 3; cytokine; Cytokines; Cytokines - genetics; Cytokines - metabolism; Drug development; Enzymes; Gelatinase B; Gene expression; Gene Expression Regulation - drug effects; Gene regulation; Genomes; Inflammation; Kinases; Matrix metalloproteinase; Mice; muscle regeneration; Musculoskeletal system; Myoblasts; Myoblasts - metabolism; MyoD protein; Myogenesis; Myostatin; Protein expression; Proteins; Signal Transduction; Skeletal muscle; Stromelysin 2; Transcription activation; Transcription factors; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Versican; United States > US; Germany; cytokine; inflammation; muscle regeneration
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13131161

Skeletal muscle regeneration after injury is a complex process involving inflammatory signaling and myoblast activation. Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) are key mediators, but their effects on gene expression in proliferating myoblasts are unclear. We performed the RNA sequencing of TNF-α treated C2C12 myoblasts to elucidate the signaling pathways and gene networks regulated by TNF-α during myoblast proliferation. The TNF-α (10 ng/mL) treatment of C2C12 cells led to 958 differentially expressed genes compared to the controls. Pathway analysis revealed significant regulation of TNF-α signaling, along with the chemokine and IL-17 pathways. Key upregulated genes included cytokines (e.g., IL-6), chemokines (e.g., CCL7), and matrix metalloproteinases (MMPs). TNF-α increased myogenic factor 5 (Myf5) but decreased MyoD protein levels and stimulated the release of MMP-9, MMP-10, and MMP-13. TNF-α also upregulates versican and myostatin mRNA. Overall, our study demonstrates the TNF-α modulation of distinct gene expression patterns and signaling pathways that likely contribute to enhanced myoblast proliferation while suppressing premature differentiation after muscle injury. Elucidating the mechanisms involved in skeletal muscle regeneration can aid in the development of regeneration-enhancing therapeutics.