Throphic action of sphingosine-1-phosphate in denervated rat soleus muscle.

The bioactive lipid sphingosine 1-phosphate (S1P) mediates a number of cellular responses, including growth and proliferation. Skeletal muscle possesses the full enzymatic machinery to generate S1P and expresses the transcripts of S1P receptors. Present work localizes the S1P1 and S1P3 receptors in skeletal muscle and shows that denervation causes down-regulation of the two receptors. The exogenous application of S1P counters the reduction of muscle mass caused by denervation, while the neutralization of the extracellular lipid with a specific anti-S1P monoclonal antibody worsens the atrophy. Our results suggest that S1P acts as a trophic factor of skeletal muscle.