Zuoguiwan Transplanted Male Bone Marrow Of Female Mice, Liver Regeneration Gene Signaling Pathway

Objective: The purpose of this research is using bioinformatics methods toobserve the influence of nourish kidney (using Zuoguiwan) on gene expression profileof that mouse bone marrow cells forming liver cells and the changes of relatedsignaling pathway, and to study the molecular mechanism of that nourishing kidneymanufacture marrow to form liver cell.Methods: The female BALB/C mice were randomly divided into nourish kidneyteam (treated by Zuoguiwan) and contrast team. After whole body irradiation with 9.0Gy ⁶⁰Coγ-rays, the female mice were injected via the tail vein with whole bonemarrow cells of homogenic male mice to establish bone marrow transplantation model.Zuoguiwan and physiological saline of 7g·kg^-1·d^-1 respectively treated three teamsafter bone marrow transplantation. By treating 6 months, all mice were sacrificed toget liver tissues. The left lobe of liver was formalin-fixed and paraffin embedded,other lobes of liver were freeze by liquid nitrogen. The difference of gene expressionprofile was detected by using mouse gene expression profile oligo-nucleotide chip.Total RNA of liquid nitrogen freezing tissues was extracted to synthetic cDNA probesthat were hybridized with gene chip. Different expressed genes were selected by theratio of hybridization signals, and the data was handled with Microsoft Access andMicrosoft Excel. The differentially expressed genes were linked to the correspondingUniGene clusters using GenBank accession numbers. Then, the UniGene clusterswere assigned to genes and their GO annotations from each of the three GOtaxonomies using LocusLink. Finally, we retrieved the KEGG database tofind thebiochemical pathways involved in the differentially expressed genes.Results: The results of gene expression profile chip hybridization showsdifferences of gene expression profile among different teams at 6 monthspost-transplantation. There're 1147 genes different expressed when nourish kidneyteam compared to contrast team. 533 genes are known and 209 genes of them arerelated to 70 biochemical pathways, such as neuroactive ligand-receptor interaction,MAPK signaling pathway, Wnt signaling pathway, cytokine-cytokine receptor interaction, purine metabolism, Jak-STAT signaling pathway, cadherin-mediated ceiladhesion, tyrosine metabolism, apoptosis, Toll-like receptor signaling pathway,oxidative phosphorylation, glycerolipid metabolism, TGF-beta signaling pathway. Thepathways related to liver regeneration are Wnt signaling pathway, MAPK signalingpathway, TGF-beta signaling pathway, Jak-STAT signaling pathway, apoptosis,Toll-like receptor signaling pathway, and so on. In these pathways, some genes asWntl, EGF, FGF2, FGF16, MAPKK1, E2F5, CSF3, Myd88, sFRP1, sFRP5, CSF2R,CNTFR, Caspase 12 are up-regulated expressed, some genes as MAPK9, Racl, GSK3,Wnt10a, IL12a, PKCγ, Akt2, Activin AR are down-regulated expressed.Conclusions: Nourish kidney (using Zuoguiwan) could promote that bonemarrow cells forming liver cells, and the mechanisms of this process mayberegulating gene expression of signaling pathway that related to liver regeneration.