Tumor necrosis factor alpha regulates myogenesis to inhibit differentiation and promote proliferation in satellite cells

• Published in: Biochemical and biophysical research communications 2021-11, Vol.580, p.35-40
• Main Authors: Shirakawa, Tomohiko, Rojasawasthien, Thira, Inoue, Asako, Matsubara, Takuma, Kawamoto, Tatsuo, Kokabu, Shoichiro
• Format: Article
• Language: English
• Subjects: Animals; Cachexia; Cachexia - metabolism; Cell Differentiation; Cell Proliferation; Humans; Male; Mice; Muscle Development; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; MyoD; NF-kappa B - metabolism; NF-κB; Organ Culture Techniques; Recombinant Proteins - metabolism; Satellite cell; Satellite Cells, Skeletal Muscle - cytology; Satellite Cells, Skeletal Muscle - metabolism; Signal Transduction; Skeletal muscle; TNF-α; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.09.067

TNF-α and NF-κB signaling is involved in the wasting of skeletal muscle in various conditions, in addition to cancer cachexia. TNF-α and NF-κB signaling promotes the expression level of muscle RING finger protein 1, a ubiquitin ligase, causing muscle degradation. Several studies have indicated that of TNF-α and NF-κB signaling suppresses muscle differentiation by reducing the levels of MyoD protein. On the other hand, TNF-α and NF-κB is required for myoblast proliferation. Thus, the role of TNF-α and NF-κB signaling in the process of myogenesis and regeneration of skeletal muscle is not completely elucidated. Here, we reported that TNF-α reduced the width of single fibers of skeletal muscle in an organ culture model. TNF-α and p65 repressed the transactivation of MyoD and suppressed myoblast differentiation. In addition, TNF-α increased the number of satellite cells, and NF-κB signaling was promoted at the proliferation stage during skeletal muscle regeneration in vivo. TNF-α and NF-κB signaling regulate myogenesis to inhibit differentiation and promote proliferation in satellite cells. •TNF-α reduces the width of single fibers of skeletal muscle in organ culture model.•TNF-α and p65 suppresses the transactivation of MyoD and myoblast differentiation.•TNF-α increases the number of satellite cells.•NF-κB signaling is activated at proliferation stage in muscle regeneration.