Suppression of sphingosine 1-phosphate lyase retards the liver regeneration in mice after partial hepatectomy.

BACKGROUND Liver regeneration is an extremely complicated process regulated by a number of signaling pathways. Sphingosine 1-phosphate (S1P), a potent bioactive lipid mediator playing crucial roles in various cellular responses through its receptors, has been attracting attention in the fields of hepatology, where S1P lyase (SPL), an irreversibly degrading enzyme of S1P, reportedly has a stimulatory role in the growth of hepatocellular carcinoma. AIM OF THE STUDY To examine whether SPL might play a stimulatory role in liver regeneration. METHOD Using in-vivo siRNA technology we inhibited SPL expression. Seventy percent of the liver was resected in mice as partial hepatectomy (PH). Liver tissue samples were collected and mRNA expression level of the SPL, IHC of the proliferating cell nuclear antigen (PCNA), protein levels of various proliferation factors and lipid measurements were performed in different groups. RESULTS The mRNA levels of SPL increased in PH mice on the 3rd day after PH surgery. When we suppressed the expression of SPL by in-vivo siRNA, we observed a significant decline of the PCNA positive cell numbers. Furthermore, the Cyclin D1 expressions and phosphorylation of ERK also were decreased in the siSPL injected PH group. CONCLUSION We verified the importance of the SPL in liver regeneration, using the mice PH model. SPL might be a potential target to facilitate liver regeneration.