Abstract

Background: Liver regeneration is an extremely complicated process that is 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 growth of hepatocellular carcinoma (HCC).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 third 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.

Highlights

  • The unique ability of the liver is to regenerate and regulate to keep its own size

  • Biosynthesis of Sphingosine 1-phosphate (S1P) is through the phosphorylation of sphingosine by sphingosine kinase 1 and 2 (SK1, SK2) which are ubiquitously expressed in most tissues, SK1 expression was predominant in lung and spleen, whereas SK2 in liver and License 4.0 (CC BY)

  • The present study showed the necessity of the S1P lyase (SPL) in liver regeneration

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Summary

Introduction

The unique ability of the liver is to regenerate and regulate to keep its own size. The regeneration of the liver occurs after either surgical resection or injury-induced cell death. The process of liver regeneration is driven by many factors including cytokines, chemokines, growth factors, and hormones [2,5,6,7,8,9]. Along with these factors, lipid mediators, such as sphingosine 1-phosphate (S1P), have been demonstrated to be involved in the liver regeneration [10,11]. 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. SPL might be a potential target to facilitate liver regeneration

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