Proinflammatory Cytokine Tumor Necrosis Factor (TNF)-like Weak Inducer of Apoptosis (TWEAK) Suppresses Satellite Cell Self-renewal through Inversely Modulating Notch and NF-κB Signaling Pathways

Cytokine Signaling in Skeletal Muscle Wasting

“…During acute ischemic injury, TWEAK is released from macrophages to induce satellite cell proliferation through activation of classical NF-kB and Notch signaling [82]. By contrast, TWEAK can suppress satellite cell selfrenewal through inversely modulating notch and NF-kB signaling pathways, as shown in a cardiotoxin injury model [20]. It is not clear how TWEAK/Fn14 activation lead to NF-kB activation, but according to Kumar et al, Fn14-induced NF-kB activation may be mediated by TRAF6, at least in a denervation model [27].…”

“…TWEAK induces muscle RING-finger protein 1 (MuRF1) expression via NF-kB activation [10] (Box 2). TWEAK also reduces satellite cell pool by inhibiting Notch signaling and activating NF-kB [20]. In addition to the NF-kB pathway, TNF-/ and TWEAK also signal to p38 MAP kinase [21,22] and the Jak/Stat pathway, which in turn upregulates the expression of atrogin-1 and MuRF1 [23].…”

TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis

“…Statistical analyses used Student's t test to compare quantitative data populations with Satellite cell cultures. Satellite cells were isolated from the hind limbs of 8-week-old mice following a protocol as described (59). Traf6 -/-cells were generated by treatment of TRAF6 scko myogenic cells with 10 ng/ml 4-hydroxytamoxifen (Sigma-Aldrich) for 48 hours.…”

“…Satellite cell proliferation was assayed by labeling the cells with EdU for 90 minutes using Click-iT EdU Cell Proliferation Assay kit (Invitrogen) as previously described (59).…”

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury

“…creased levels of proinflammatory cytokines in the skeletal muscle have been emerging as potential contributors to muscle insulin resistance (13,14), impaired oxidative metabolism (35,36), increased fibrosis (39), and impaired regenerative capacity (27,32). Given that paralyzed muscle presents with extreme atrophy (11), impaired muscle metabolism (16,26), and impaired regenerative capacity (1) shortly after SCI, it is important to consider the impact of skeletal muscle inflammation on these reported muscle pathologies.…”