Screening And Functional Analysis Of Proteins Related To Bone Marrow Mesenchymal Stem Cells Activating Residual Hepatocyte Regeneration

Objective: BMSCs(bone marrow mesenchymal stem cells)can improve liver function by activating residual hepatocyte regeneration as an effective treatment of acute liver failure,but the mechanism is unclear.By using proteomics technology and bioinformatics analysis to find the key protein which participated the process that BMSCs activated residual hepatocyte regeneration in acute liver failure.Methods: Establish a animal model of acute liver failure using rats induced by Dgalactose(DGa In).At 12 h after DGa In treatment,the rats went intravenous vein BMSCs transplantation,200 mg of liver tissue was taken from the survival and dead groups,and quantitative proteomics technology was used to screen proteins.Bioinformatics analysis including Go(gene ontology)analysis,KEGG(Kyoto Encyclopedia of genes and genes)pathway analysis,protein interaction(PPI)analysis was carried out for differentially expressed proteins.Functional analysis of the key proteins related to the process of BMSCs activated residual hepatocyte regeneration were carried on by searching Uni Prot database and published literatures.Results: ? After analyzing and comparing the identified proteins from the survival and death group,112 proteins had significant differences.Compared with the dead group,there were 43 up-regulated proteins and 69 down-regulated proteins in the survival group.The key proteins,such as,STAT3?IGF-1?SPARC?MFG-E8,participated the process that BMSCs activated hepatocyte regeneration.? GO analysis was carried on by Blast2 GO,in order to figure out that these differentially expressed proteins are mainly involved in "metabolic process","biological regulation","regulation of biological process","signaling" and "immune system process","cellular component organization or biogenesis" in biological process;"binding","molecular function regulator ","nucleic acid binding transcription factor activity" and "signal transducer activity" in molecular function;"cell","cell part","organelle","membrane" and "extracellular region part " in cellular component.(KEGG analysis was carried on by KAAS(KEGG Automatic Annotation Server),in order to figure out these differentially expressed proteins are mainly involved in "P13-Akt signaling pathway","protein digestion and absorption","Epstein-Barr virus infection ","protein processing in endoplasmic reticulum ","RNA transport " and "Ribosome biogenesis in eukaryotes� " signaling pathways.Conclusion:(1)STAT3,IGF-1,SPARC,MFG-E8 are key proteins in process of bone marrow mesenchymal stem cells activating hepatocyte regeneration in acute liver failure.In protein expression of the survival group,STAT3 up-regulation,IGF-1?SPARC?MFGE8 down-regulation.(2)STAT3,IGF-1,SPARC,MFG-E8 participate in the biological process,such as single-organism process,regulation of biological process and development process.They all took an important role in binding molecular process.(3)STAT3,IGF-1 both attended in signaling pathways regulating pluripotency of stem cells,HIF-1 signaling pathway,they may have intensive access to the mechanism of MSCs treatment on acute liver failure.