| First Author | Marchildon F | Year | 2016 |
| Journal | Cell Death Dis | Volume | 7 |
| Pages | e2109 | PubMed ID | 26913600 |
| Mgi Jnum | J:318337 | Mgi Id | MGI:6859265 |
| Doi | 10.1038/cddis.2016.4 | Citation | Marchildon F, et al. (2016) CCAAT/enhancer binding protein beta protects muscle satellite cells from apoptosis after injury and in cancer cachexia. Cell Death Dis 7:e2109 |
| abstractText | CCAAT/enhancer binding protein beta (C/EBPbeta), a transcription factor expressed in muscle satellite cells (SCs), inhibits the myogenic program and is downregulated early in differentiation. In a conditional null model in which C/EBPbeta expression is knocked down in paired box protein 7+ (Pax7+) SCs, cardiotoxin (CTX) injury is poorly repaired, although muscle regeneration is efficient in control littermates. While myoblasts lacking C/EBPbeta can differentiate efficiently in culture, after CTX injury poor regeneration was attributed to a smaller than normal Pax7+ population, which was not due to a failure of SCs to proliferate. Rather, the percentage of apoptotic SCs was increased in muscle lacking C/EBPbeta. Given that an injury induced by BaCl2 is repaired with greater efficiency than controls in the absence of C/EBPbeta, we investigated the inflammatory response following BaCl2 and CTX injury and found that the levels of interleukin-1beta (IL-1beta), a proinflammatory cytokine, were robustly elevated following CTX injury and could induce C/EBPbeta expression in myoblasts. High levels of C/EBPbeta expression in myoblasts correlated with resistance to apoptotic stimuli, while its loss increased sensitivity to thapsigargin-induced cell death. Using cancer cachexia as a model for chronic inflammation, we found that C/EBPbeta expression was increased in SCs and myoblasts of tumor-bearing cachectic animals. Further, in cachectic conditional knockout animals lacking C/EBPbeta in Pax7+ cells, the SC compartment was reduced because of increased apoptosis, and regeneration was impaired. Our findings indicate that the stimulation of C/EBPbeta expression by IL-1beta following muscle injury and in cancer cachexia acts to promote SC survival, and is therefore a protective mechanism for SCs and myoblasts in the face of inflammation. |
