| First Author | Ogura Y | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 49 | Pages | 35159-69 |
| PubMed ID | 24151074 | Mgi Jnum | J:207209 |
| Mgi Id | MGI:5554663 | Doi | 10.1074/jbc.M113.517300 |
| Citation | Ogura Y, et al. (2013) Proinflammatory cytokine tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) suppresses satellite cell self-renewal through inversely modulating Notch and NF-kappaB signaling pathways. J Biol Chem 288(49):35159-69 |
| abstractText | Satellite cell self-renewal is an essential process to maintaining the robustness of skeletal muscle regenerative capacity. However, extrinsic factors that regulate self-renewal of satellite cells are not well understood. Here, we demonstrate that TWEAK cytokine reduces the proportion of Pax7(+)/MyoD(-) cells (an index of self-renewal) on myofiber explants and represses multiple components of Notch signaling in satellite cell cultures. The number of Pax7(+) cells is significantly increased in skeletal muscle of TWEAK knock-out (KO) mice compared with wild-type in response to injury. Furthermore, Notch signaling is significantly elevated in cultured satellite cells and in regenerating myofibers of TWEAK-KO mice. Forced activation of Notch signaling through overexpression of the Notch1 intracellular domain (N1ICD) rescued the TWEAK-mediated inhibition of satellite cell self-renewal. TWEAK also activates the NF-kappaB transcription factor in satellite cells and inhibition of NF-kappaB significantly improved the number of Pax7(+) cells in TWEAK-treated cultures. Furthermore, our results demonstrate that a reciprocal interaction between NF-kappaB and Notch signaling governs the inhibitory effect of TWEAK on satellite cell self-renewal. Collectively, our study demonstrates that TWEAK suppresses satellite cell self-renewal through activating NF-kappaB and repressing Notch signaling. |
