Study On The Regulation Of Crh,Bcr, Rank, ERBB2-ERBB3and IGF-1Signaling Pathway In Hepatocyte Survival During Rat Liver Regeneration

After partial hepatectomy or injury, a variety of cell signalings are originated to participate liver regeneration (LR). In order to understand the mechanism underlying the process and signaling of hepatocyte survival during rat liver regeneration, we respectively used Ingenuity Pathway Analysis9.0(IPA) to determine signaling pathways and genes associated with cell survival, Rat Genome2302.0Array to determine the expression level of these genes,-log(p-value) and f-test to determine cell survival situation, the results showed that hepatocyte survival activities regulated by CRH, IGF-1and BCR signaling pathways in PH and those of SO group were very significant difference(P<0.01), hepatocyte survival activities regulated by RANK and ErbB2-ErbB3signaling pathways in PH and SO group were significant difference(P≤0.05), the other signaling pathways were not found to be significant between PH and SO group.Then, this article used Expression profile function (Ep) to calculate the gene expression change of signaling pathways, it showed that the Ep value of signal transduction activity of Ras/ERK branch in BCR, RANK and IGF-1signaling pathway, Gaq and Gas branch in CRH signaling pathway, PI3K/AKT branch in BCR signaling pathway were significantly higher than the control group in the progression phase of LR. The Ep value of PI3K/AKT branch in RANK and IGF-1signaling pathway were significantly higher in the priming and progression phase. The Ep value of PLCy branch in BCR signaling pathway, JAK/STAT and PI3K/AKT branch in ErbB2-ErbB3signaling pathway were significantly higher in the progression and termination phase. The Ep value of Ras/ERK branch in ErbB2-ErbB3signaling pathway and JAK/STAT branch in IGF-1signaling pathway were significantly higher throughout the entire course of LR.Finally, this article used network techniques to analyze the regulatory branches and their manner of signaling pathways, the result showed that hepatocyte survival of Ras/ERK branch in BCR and RANK signaling pathway, Gaq and Gas branch in CRH signaling pathway, and PI3K/AKT branch in BCR signaling pathway was strengthened in the progression phase of LR. Hepatocyte survival of PI3K/AKT branch in RANK and IGF-1signaling pathway was enhanced in the priming and progression phase. Hepatocyte survival of PLCy branch in BCR signaling pathway, JAK/STAT and PI3K/AKT branch in ErbB2-ErbB3signaling pathway was reinforced in the progression and termination phase. Hepatocyte survival of Ras/ERK branch in ErbB2-ErbB3signaling pathway and JAK/STAT branch in IGF-1signaling pathway was increased throughout the entire course of LR.Conclusion:forty six cell survival signaling pathways were involved in rat liver regeneration, in which CRH, BCR, RANK, ErbB2-ErbB3and IGF-1signaling pathways and their six branches played a major role in promoting hepatocyte survival during liver regeneration.