Study on activity of the signaling pathways regulating hepatocyte differentiation during rat liver regeneration

Abstract

To understand the mechanism of hepatocyte differentiation during rat liver regeneration (LR) at the gene transcription level, Rat Genome 230 2.0 Array was used to determine the gene expression changes of hepatocytes. Then the genes associated with cell differentiation and their signaling pathways were searched by NCBI, QIAGEN and KEGG webs, and their signaling activities were calculated by spectral function Ep(t) based on the expression profiles. The key genes associated with the signaling pathways and cell differentiation were analyzed and verified by the same kind extraction method. The mechanism of hepatocyte differentiation during rat LR was analyzed by Ingenuity Pathway Analysis 9.0 (IPA). The results showed that 42 signaling pathways regulated cell differentiation and the Ep(t) values of IL-9 signaling pathway and its JAK/STAT and PI3K/AKT branches, PEDF signaling pathway and its NF-κB and Ras/ERK branches were significantly increased in the progression phase (6–72 h after partial hepatectomy [PH]) of rat LR, and the Ep(t) values of hepatocyte differentiation were also significantly increased. ERK/MAPK signaling pathway was significantly increased in the priming (0.5–6 h after PH) and progression phase, and hepatocyte differentiation were also significantly increased. In conclusion, among the 42 signaling pathways that regulated cell differentiation, the signaling activity of IL-9 signaling pathway and its JAK/STAT and PI3K/AKT branches, PEDF signaling activity and its NF-κB and Ras/ERK branches, and ERK/MAPK signaling activity were significantly increased and promoted hepatocyte differentiation in rat LR. Meanwhile, the expression of MYC involved in mentioned signaling pathways and expression of AGT, BCL2, IL10, CCND1, PLAT, and NF1 related to cell differentiation were increased significantly.