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Publication : TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-κB activation and impairment of IGF-1 signaling pathway.

First Author  Zhao Q Year  2015
Journal  Biochem Biophys Res Commun Volume  458
Issue  4 Pages  790-5
PubMed ID  25686491 Mgi Jnum  J:220481
Mgi Id  MGI:5634858 Doi  10.1016/j.bbrc.2015.02.026
Citation  Zhao Q, et al. (2015) TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-kappaB activation and impairment of IGF-1 signaling pathway. Biochem Biophys Res Commun 458(4):790-5
abstractText  Cachexia or muscle wasting is a common condition that occurs in many chronic diseases. The wasting conditions are characterized by increased levels of TNF-alpha which was also known as cachectin in the past. But how TNF-alpha exerts its cachetic effects remains controversial. To clarify this issue, we investigated the impact of TNF-alpha on C2C12 cell myogenic differentiation. Our results demonstrate that myotube formation was completely inhibited by TNF-alpha when added to differentiating C2C12 myoblasts. The inhibitory effect of TNF-alpha on differentiation was accompanied by activation of NF-kappaB and down regulation of myogenin and Akt. Importantly, TNF-alpha's effect on differentiation was abolished when IGF-1 was added to the culture. IGF-1 treatment also inhibited NF-kappaB reporter activity and restored Akt levels. Our data suggest that TNF-alpha inhibits myogenic differentiation through NF-kappaB activation and impairment of IGF-1 signaling pathway. The reversal of TNF-alpha induced inhibition of myogenesis by IGF-1 may have significant therapeutic potential.
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