CCAAT/enhancer binding protein beta protects muscle satellite cells from apoptosis after injury and in cancer cachexia.
Cell Death Dis
; 7: e2109, 2016 Feb 25.
Article
em En
| MEDLINE
| ID: mdl-26913600
ABSTRACT
CCAAT/enhancer binding protein beta (C/EBPß), 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/EBPß 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/EBPß 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/EBPß. Given that an injury induced by BaCl2 is repaired with greater efficiency than controls in the absence of C/EBPß, we investigated the inflammatory response following BaCl2 and CTX injury and found that the levels of interleukin-1ß (IL-1ß), a proinflammatory cytokine, were robustly elevated following CTX injury and could induce C/EBPß expression in myoblasts. High levels of C/EBPß 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/EBPß expression was increased in SCs and myoblasts of tumor-bearing cachectic animals. Further, in cachectic conditional knockout animals lacking C/EBPß in Pax7+ cells, the SC compartment was reduced because of increased apoptosis, and regeneration was impaired. Our findings indicate that the stimulation of C/EBPß expression by IL-1ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteína beta Intensificadora de Ligação a CCAAT
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article