Sphingosine 1-Phosphate (S1P) participates in migration of bone marrow (BM)-derived mesenchymal stem cells (BMSCs) towards damaged liver via up-regulation of S1P receptor 3 (S1PR3) during mouse liver fibrogenesis.But the molecular mechanism is still unclear.HuR,as an RNA-binding protein,regulates tumor cells motility.Here,we examined the role of HuR in migration of human BMSCs (hBMSCs) in liver fibrosis.Results showed that HuR mRNA level was increased in human or mouse fibrotic livers,and correlated with S1PR3 mRNA expression.Using immunofluorescence,we found that HuR mainly localized in the nuclei of hepatocytes and non-parenchymal cells in normal livers.However,in fibrotic livers,we detected an increased HuR cytoplasmic localization in non-parenchymal cells.In chimeric mice of BM cell-labeled by EGFP,significant numbers of EGFP-positive cells (BM origin) were positive for HuR in fibrotic areas.Meanwhile,HuR-positive cells were also positive for α-SMA (myofibroblasts).In vitro,S1P induced hBMSCs migration via S1PR3 up-regulation.HuR involved in S1P-induced hBMSCs migration and increased stabilization of S1PR3 mRNA via competing with miR-30e.RNA immunoprecipitation showed that HuR interacted with S1PR3 mRNA 3UTR.Moreover,S1P resulted in phosphorylation and cytoplasmic translocation of HuR via S1PR3 and p38MAPK.Furthermore,we transplanted EGFP+ BMSCs with or without HuR siRNA into carbon tetrachloride-treated mice,and found that knockdown of HuR inhibited the migration of BMSCs towards injured livers by flow-cytometric analysis in vivo.Conclusions:We identified a positive feedback regulation mechanism between HuR and S1PR3 in S 1 P-induced BMSCs migration.HuR participates in up-regulation of S 1PR3 induced by S1P.S1P results in phosphorylation and translocation of HuR via S1PR3.Our results provide a new regulatory manner to the mechanism of liver fibrogenesis.