Tumor necrosis factor-α exerts pro-myogenic action in C2C12 myoblasts via sphingosine kinase/S1P2 signaling

In this study, we report that low doses of tumor necrosis factor-α (TNFα) promote myogenesis in C2C12 myoblasts. Moreover, the cytokine increased sphingosine kinase (SphK) activity and induced SphK1 translocation to membranes. The inhibition of SphK functionality by various approaches abrogated the pro-myogenic effect of TNFα. Moreover, silencing of S1P2 impaired the positive action of TNFα on myogenesis. These results represent the first evidence that SphK/S1P2 axis is required for the regulation of myogenesis by TNFα. In view of the physiological role of TNFα in muscle regeneration, the present finding reinforces the notion that SphK/S1P2 signaling is critically implicated in myogenesis.