Y-box Binding Protein 1 Regulates Proliferation And Synthesis Of Extracellular Matrix Of Hepatic Progenitor Cells

Objective: to explore the roles of Y-box protein-1(YB-1)in hepatic progenitor cells(HPC)and the detailed molecular mechanisms when liver regeneration and fibrogenesis develops.Methods : Immunofluorescence assays and immunohistochemistry technology were used to detect the protein expression in specific cells.After the expression of YB-1 in HPC,cell counting kit and flow cytometry were utilized to detect cell proliferation and cell cycles.RT-PCR and Western blot assays were performed to determine the m RNA and protein expression.Chromatin immunoprecipitation assays were introduced to determine the target genes of YB-1.Luciferase reporter assays were conducted to assess the regulatory effect of YB-1 on its target gene.Results(1)The expression of YB-1is elevated in livers of patients infected with chronic viral hepatitis B and the expression level correlated with the severity of liver fibrosis.(2)YB-1 directly binds to the promoter of Gli2 and regulate its transcriptional activity.YB-1 knockdown suppress the proliferation of HPC through down-regulated Hedgehog signaling.(3)YB-1 knockdown promotes the expression of extracellular matrix in HPC.PDGFR-? is a target gene of YB-1and YB-1 negatively regulates PDGFR-? promoter activity in HPCs.(4)PDGFR-? can regulate the expression of collagen I by ERK/p90 RSK signaling and disruption of the signaling pathway with PDGFR-? inhibitor or ERK1/2 inhibitor abolished the regulatory effect of PDGFR-? on collagen I expression in HPC.Conclusion: YB-1 can promote the proliferation of HPC via Hedgehog signaling and negatively regulate the expression of extracellular matrix through PDGFR-? /ERK/p90 RSK signaling.