Figure 4

Intervention at the miRNA level can rescue the effect of TNF-α on myotube formation. (A) TNF-α partly mediates its negative effect on myotube formation through interfering at the miRNA level. TNF-α stimulates expression of miR-155 which is downregulated during myoblast differentiation. Overexpression of miR-155 blocked myotube formation. TNF-α downregulated miR-503 expression during myoblast differentiation. miR-503 expression was upregulated during myotube formation. Simultaneous inhibition of miR-155 and overexpression of miR-503 rescued the inhibitory effect of TNF-α on myotube formation. Grey indicates validated targets Mef2a [36] and Cdc25a [38]. (B) Schematic overview of the regulation of miRNA expression by TNF-α or IGF1 during skeletal myoblast differentiation. The width of the blue arrows or lines indicate the relative quantity of miRNAs regulated by TNF-α or IGF1 in skeletal myoblast differentiation. TNF-α mainly inversely regulated miRNAs expression associated with myoblast differentiation. IGF1 promoted and antagonised myogenesis associated miRNA expression. Few miRNAs are specifically regulated by TNF-α or IGF1, and in turn, part of these miRNAs are counteracted by TNF-α or IGF1.