S1P was first shown to stimulate rat hepatic stellate cell proliferation, suggesting that S1P could be a pro-fibrotic factor in the liver48; several studies clearly showed that this pro-fibrotic effect is regulated thorough the S1P receptors S1P1, S1P2, and S1P3 on hepatic stellate cells46,49–52, suggesting that depletion of S1P by SPHK inhibitors could be effective for liver fibrosis. This evidence concerns the gene SPHK1 and Hepatic fibrosis.