FGF Pathway On Regulation Of DNA Synthesis In Rat Liver Regeneration And Hepatocytes

Liver regeneration (LR) is a complex and coordinated physiological process. And it is completedcollaboratively by all the residual liver cells,,which includes many important physiological activities suchas activation of cytokines and growth factors, cell proliferation and apoptosis, carbohydrate metabolism,cell migration, liver structure reconstruction and so on. Liver cells (of hepatocytes, HC) are the mostimportant liver parenchymal cells, because they account for70%-80%of the total number of liver cells. Itgoes without saying that liver cells play an important role in liver regeneration. In order to describe theexpression of fibroblast growth factor (FGF) signaling pathway in genomics and its correlation with ratliver regeneration, in addition, to understand the similarities and differences of FGF signaling pathwayrelated genes in the gene transcription level between rat regenerate liver organization and cells, we used ratgenome chip Rat Genome2302.0to detect the FGF signaling pathway related genes, DNA synthesisrelated genes, expression profiling of DNA synthesis-related genes regulated by FGF signaling pathway.And the real-time quantitative-polymerase chain reaction (RT-PCR)were used to confirm the reliability ofthe results. Studies showed that FGF signaling pathway, DNA synthesis and the DNA synthesis regulatedby FGF signaling pathway contained319,917and107genes respectively. Rat Genome2302.0chipscontained194,763and87respectively. Meaningful expressing genes in liver regeneration were61,381and40respectively. Meaningful expressing genes in liver cells were76,365and37respectively. In addition,using BLAST software to analysis the unknown liver regeneration gene homology on the Affymetrix chipwe found that homologous genes of FGF signaling pathway, DNA synthesis, DNA synthesis-related genesregulated by FGF signaling pathway were28,65,5respectively in rat regenerate liver. Homologous genesin liver cells were10,45and6respectively. Then, spectral function (Et) was used to calculate theexpression changes of related genes..And their cell proliferation activities showed that in rat regenerateliver, activities of channels2,3, and9enhanced in initiation and progress stage of rat liver.The activities ofDNA synthesis and DNA synthesis regulated by FGF signaling pathway also enhanced in the initiation andprogress stage. What′s more,they had a positive correlation with signal transduction activity. In liver cells,signal transduction activities of channels2,9enhanced in initiation and progress stage; signal transductionactivities of channels3,16enhanced during the whole regeneration progress; signal transduction activities of pathway4,6enhanced in progress and termination stage. Activities of DNA synthesis and DNA synthesisregulated by FGF signaling pathway enhanced significantly in the whole liver regeneration progress, andthey also had a positive correlation with their signal transduction activities. Finally, we used theinformation entropy of the IG (information gain) method to excavate key genes and used Pathway Studio7.0software to analysis the mechanism of key genes. The results showed that in rat liver regeneration,key genes Dusp1, Nifkbia in channel2, key genes Dusp1, Mapk3in channel3, key genes Ccnd1, Pak3inchannel9enhanced MAPK, PI3K/Akt, ERK1/2and PLCγ and other ways to enhance the expression ofkey genes Jun, Myc, Fos and other related genes to promote DNA synthesis. In liver cells, key genes Dusp1,Nifkbia in channel2, key genes Dusp1, Mapk3in channel3, key genes Ccnd1, Pak3in channel9, keygenes Smn1,Akt3in channel4,6,16enhanced the expression of key genes and promoted DNAsynthesis. Conclusion: in rat regenerate liver, there were three FGF signaling pathway had a positivecorrelation with the enhancements of DNA synthesis activity. In rat liver cells, there were six FGFsignaling pathway had a positive correlation with the enhancements of DNA synthesis activity.