肝纤维化的共同表现是肝肌成纤维细胞在肝细胞坏死部位的大量聚集，骨髓间充质干细胞（BMSCs）是其重要来源之一。本课题组工作表明磷酸鞘胺醇（S1P）能以S1P受体3（S1PR3）依赖的方式趋化BMSCs向肝损伤部位迁移，造成肝脏病变的进一步恶化，但其作用机制尚待深入研究。HuR是一种重要的转录后调控因子，在肝纤维化的发生中的作用鲜有报道，可能是肝纤维化的重要参与者。通过前期预实验，申请者发现：用S1P处理BMSCs不影响HuR的表达，但可增高细胞浆HuR水平；沉默HuR明显降低S1PR3 mRNA表达，阻断S1P诱导的BMSCs迁移过程；HuR可以与S1PR3 mRNA结合。本课题拟以BMSCs为研究对象，以HuR及S1PR3为靶分子，结合细胞学和动物学实验，系统、完整地研究HuR调节S1PR3表达并参与S1P诱导的BMSCs迁移的分子机制，为肝纤维化发病机制的研究提供新的视角。

Hepatic myofibroblasts play a central role in the pathogenesis of liver fibrosis and a high proportion of myofibroblasts in the fibrotic liver are of Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) origin. In our previous study, we demonstrated that BMSCs can migrate to the damaged liver, mediated by endogenous sphingosine 1-phosphate (S1P) in a S1PR3-depended way. HuR, as a RNA-binding protein, is important for the pathogenesis of liver fibrosis development. Our preliminary results indicate that knockdown of HuR decreased S1PR3 mRNA expression and blocked S1P-induced BMSCs migration. Treatment of BMSCs with S1P did not affect HuR expression, but increased HuR level in cytoplasm. RNA immunoprecipitation showed that HuR could bind with S1PR3 mRNA. We will further explore the mechanism of HuR regulates S1PR3 expression and mediates S1P-induced cell migration in BMSCs. Our results will find a new regulation manner to the mechanism of liver fibrosis occurrence.