The Research On The Promotion Of Hepatocyte Migration Of HGF Signaling Pathway During Liver Regeneration

Liver regeneration (LR) involves cell proliferation, differentiation, regulation of cell migration, aswell as organizational structure and functional reconstruction of a series of physiological and biochemicalactivities. Cell migration is closely related to extracellular matrix (ECM), cell junction, cytoskeleton andmembrane proteins. HGF signaling pathway could induce cell proliferation, dispersion, migration andorgan morphogenesis and angiogenesis, and plays an important regulatory role in liver regeneration. Inorder to clarify the regulatory effect of hepatocyte growth factor (HGF) signaling pathway on hepatocytemigration during rat liver regeneration, Rat Genome2302.0Array was used to detect the expressionprofiles of HGF signaling pathway-, cell migration-, HGF signal pathway-regulated cell migration-relatedgenes, and real-time quantitative RT-PCR was applied to validate the reliability of chip detection results. Itshowed that94,462and40genes were involved in HGF signaling pathway, cell migration and HGFsignaling pathway-regulated cell migration, respectively, among which80,445and40genes were includedin Rat the Genome2302.0Array. In regenerating livers,15,143and16LR-realted genes were foundinvolved in above three biological processes, respetively, and25,180and17LR-realted genes were forhepatocytes from regenerating livers. BLAST was applied to analyze the homology of unknown geneswhich is related to liver regeneration. In regenerating livers, many homologous genes involved in HGFsignaling pathway (including14known genes and14homologous genes), cell migration-related genes(including33known genes and35homologous genes) and HGF signaling pathway-regulated cellmigration (including4known genes and4homologous genes) were found. In hepatocytes fromregenerating livers, many genes also involved in HGF signaling pathway (including9known genes and9homologous genes), cell migration-related genes (including45known genes and55homologous genes)and HGF signaling pathway-regulated cell migration (including7known genes and7homologous genes).Expression profile function (Et) was applied to analyze changes of gene expression and indicate the changeof cell migration activity. It showed that, in regenerating livers, activity of path14and15were increased inthe beginning and advanced stage of LR; activity of cell migration were increased at2-12and72h after PH,and the activity of HGF signal pathway-regulated cell migration-related were increased at2-12,30and72h. In hepatocytes, activity of path4,5,8,9,12,14and15were increased in the whole liver regeneration;activity of cell migration were increased at6-168h after PH, and the activity of HGF signalpathway-regulated cell migration-related were increased at24-120h.X2-test was used to calculate eachgene expression differences (R) values between partial hepatecotomy group and sham opration group. Theresulte showed that, in rat regenerating liver, Jun, Rras2, Rac1, Timp1, Ceacam1and Itga7were key genesin HGF signaling pathway. Timp1and Ceacam1were key genes of cell migration. In hepatocytes, Ceacam1,Jun, Kras, Met and Timp1were key genes in HGF signaling pathway. Ceacam1, Plat and Met were keygenes of cell migration. Then using Resnet Core1.2database of Pathway Studio7.0software to analysis theregulatory mechanism of key genes, in rat regenerating liver, path14through key genes Rras2'shomologous genes AI548708and Ceacam1, path15through the key genes Rac1and timp1promoted Itgamand Itgb8's the homologous gene BG669893to express integrin, which directly involved the process of cellmigration. In hepatocytes, Path4,8,5and9through key genes Met and Kras' homologous gene BF389527,path12through the key genes Met and Pik3r3and significantly up-regulated genes Akt3and Pak1,activated c-jun and ATF2, which promoted cell migration by regulating of expression of key genes Plat,Met and so on. Path14through key genes Rras2's homologous genes AI548708and Ceacam1, path15through the key genes Rac1and timp1promoted Itgam and Itgb8the homologous gene BG669893toexpress integrin, which directly involved the process of cell migration. Conclusion: two main paths andseven paths of HGF pathway respectively enhance in signal transduction and cell migration during liverregeneration of rat liver tissue and hepatocytes.