Aim: 

Sphingosine 1-phosphate (S1P) is a bioactive lipid known to control cell growth that was recently revealed to act as a trophic factor of skeletal muscle, reducing the progress of denervation atrophy. We aimed to investigate whether S1P is involved in skeletal muscle regeneration after extensive injury.

Methods and Results: 

The postnatal ability of skeletal muscle to grow and regenerate resides in a population of resident stem cells, the satellite cells. Immunofluorescence analysis demonstrated that S1P₁ and S1P3, S1P-specific receptors, are localized in quiescent satellite cells. During soleus muscle regeneration, induced by injecting bupivacaine, expression of S1P₁ receptor progressively increased between 3 and 7 days after degeneration, while S1P₃ progressively decreased up to adult levels. S1P₁ and S1P₃ receptors had a diffuse localization at 3 days, whereas at 7 days they prevalently decorated cell and nuclei membranes, as in adult fibres. The presence of exogenously added S1P during regeneration caused a significant increase of the mean cross sectional area of regenerating fibres (+14%) and of activated Akt level.

Preliminary results indicate that during the regenerating process S1P₁ receptor exerts a modulatory role by controlling muscle fibre growth.

Conclusion: 

These results indicate that S1P signaling participates in the regenerative processes of skeletal muscle.