Study On The Stimulatory Role Of NF-κB Signaling Pathway In Hepatocyte Proliferation During Rat Liver Regeneration

The liver has an important physiological functions and a very strong regeneration. Liver regenerationdamaged by physical, chemical, and biological factors is the progress which contains cell activation,proliferation, dedifferentiation, redifferentiation, transdifferentiation of residual liver cells compensates forthe loss of liver tissue and restores biological functions of liver. On the other hand, Nuclear factor kappaB(NF-κB) signal pathway involves in regulating genes transcription of immune responses, inflammation, cellproliferation, lymphocyte development and so on. In order to understand the regulation function of NF-κBpathway in rat liver regeneration and hepatocytes prolif eration on the gene transcription level. Using RatGenome2302.0Array detected expression profiles of NF-κB pathway-related genes, cell proliferation-related genes, and NF-κB pathway regulation of cell proliferation-related genes. Real-time-polymerasechain reaction (RT-PCR) had confirmed the reliability of this chip. The results showed that NF-κBpathway,cell proliferation and NF-κB pathway regulation of cell proliferation-related genes respectivelywere238,1680and118. Rat Genome2302.0Array contained197,1314and118genes. In rat regeneratingliver, the numbers of genes which the three happened to express significant changes and belonged to theliver regeneration-related genes were79,423and56. In hepatocytes of liver regeneration, the numbers ofthese three happened to express significant changes and belonged to the liver regeneration-related geneswere83,484and58. In addition, with BLAST software analized the unknown genes homology inAffymetrix chip of liver regeneration, in rat regenerating liver,19new genes and18known genes ofNF-κB pathway-related genes were homology,86new genes and78known genes cell proliferation-relatedgenes were homologous,6new genes and6known genes of NF-κB pathway regulation of cellproliferation-related genes were homologous. In hepatocytes,21new genes and18known genes of NF-κBpathway-related genes were homology;104new gene and91known genes of cell proliferation-relatedgenes were homologous;11new genes and10known genes of NF-κB pathway regulation of cellproliferation-related genes were homologous. Use Etanalized gene expression changes and respectivelyindicated cell proliferation. It showed that, in the rat regenerating liver, Path1,12and13increased signaltransmission activaty in initiation and progressing phase of rat liver regeneration as well as path5and6inprogressing phase. The activity of cell proliferation enhanced in2-72h after PH, and cell proliferation in the downstream of NF-kB signaling pathways enhanced6-72h after PH. In hepatocytes, Path1increasedsignal transmission activity in initiation and progressing phase of rat liver regeneration as well as path12inprogressing phase and path13in progressing and termination phase. In the whole of rat liver regeneration,hepatocytes proliferation and the proliferation in the downstream of NF-κB signaling pathways enhanced.T-Statistic method was used to calculate each gene expression differences T values in the rat liverregeneration group and sham opration group, The resulte showed that, in regenerating liver, Lbp, Egfr, Egf,Rras2, Rac1, Cxcl16, Tnfrsf12a, Kdr, Fgr, Tnfrsf1a and so on were key genes in NF-κB pathway. Jun, Myc,Ldha and Bcl3were key genes of cell proliferation. In hepatocytes, Tnfrsf12a, Kras, Cxcl12, Gnai2, Nfkb1,Gnai1and so on were key genes in NF-κB pathway, Ccnd1,Dusp1were key genes of cell proliferation.Then using Resnet Core1.2database builted in Pathway Studio7.0software to analysis the mechanism ofkey genes, in rat regenerating liver, path1through key gene Tnfrsf12a, path5and6through key gene Lbp,path12through key gene Rras2's homologous gene AI548708and path13through key gene Cxcl16, Fgr,and Cxcr4activited NF-κB, the latter promoted cell proliferation by enhancing key genes Jun, Myc, Ldha,Bcl3and other related genes expression. In hepatocytes, path1through key gene Tnfrsf12a, path12through key gene kras and path13through key gene Cxcl12and Gnai1enhance NF-κB activity, the latterby adjusting the key genes Ccnd1, Dusp1and other related genes promote hepatocytes proliferation.Conclusion: Five and three channels of NF-κB pathway respectively enhanced the signal transmission andcell proliferation activity in rat regenerating liver and hepatocytes, in addition, there was a positivecorrelation.