Comparative Analysis of the Role of ERK1/2 Signaling Pathway in Regulating Cell Proliferation of Rat Liver Regeneration and Rat Acute Hepatic Failure

AbstractTo explore the role of the integrin signaling pathway in hepatocytes during rat liver regeneration, the integrin signaling pathway-related gene expression profile in hepatocytes of regenerative liver was detected using Rat Genome 230 2.0 array. The chip data showed that 265 genes of the integrin signaling pathway were included by Rat Genome 230 2.0 array and 132 genes showed significant expression changes in hepatocytes of regenerative liver. The numbers of up-, down- and up/down-regulated genes were 110, 15 and 7 respectively. In addition, bioinformatics and systems biology methods were used to analyze the role of the integrin signaling pathway in hepatocytes. The analysis of gene synergy value indicated that paths 1, 8, 12, and 15 promoted hepatocyte proliferation at the priming phase of liver regeneration; paths 1, 3, 8, and 12–15 enhanced hepatocyte proliferation at the progressing phase; paths 11 and 14 promoted hepatocyte proliferation, while paths 12 and 13 reduced hepatocyte proliferation at the terminal phase. Additionally, the other 8 paths (2, 4, 5–7, 9–10, and 16) were not found to be related to liver regeneration. In conclusion, 132 genes and 8 cascades of the integrin signaling pathway participated in regulating hepatocyte proliferation during rat liver regeneration.

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Expression profiles uncover the relationship between erythropoietin and cell proliferation in rat hepatocytes after a partial hepatectomy

Cellular & Molecular Biology Letters ◽

10.2478/s11658-014-0198-0 ◽

2014 ◽

Vol 19 (3) ◽

Cited By ~ 4

Author(s):

Jihong Zhang ◽

Yajuan Yang ◽

Tingting He ◽

Yunqing Liu ◽

Yun Zhou ◽

...

Keyword(s):

Cell Proliferation ◽

Liver Regeneration ◽

Signaling Pathway ◽

Partial Hepatectomy ◽

Rat Liver ◽

Target Genes ◽

Expression Profiles ◽

Synergetic Effect ◽

Rat Liver Regeneration ◽

Percoll Density Gradient Centrifugation

AbstractErythropoietin (EPO) has a beneficial effect on hepatic cell proliferation during liver regeneration. However, the underlying mechanism has not yet been elucidated. To uncover the proliferation response of EPO in rat liver regeneration after partial hepatectomy (PH) at the cellular level, hepatocytes (HCs) were isolated using Percoll density gradient centrifugation. The genes of the EPO-mediated signaling pathway and the target genes of the transcription factor (TF) in the pathway were identified in a pathway and TF database search. Their expression profiles were then detected using Rat Genome 230 2.0 Microarray. The results indicated that the EPO-mediated signaling pathway is involved in 19 paths and that 124 genes participate, of which 32 showed significant changes and could be identified as liver regeneration-related genes. In addition, 443 targets regulated by the TFs of the pathway and 60 genes associated with cell proliferation were contained in the array. Subsequently, the synergetic effect of these genes in liver regeneration was analyzed using the E(t) mathematical model based on their expression profiles. The results demonstrated that the E(t) values of paths 3, 8, 12 and 14–17 were significantly strengthened in the progressing phase of liver regeneration through the RAS/MEK/ERK or PI3K/AκT pathways. The synergetic effect of the target genes, in parallel with target-related cell proliferation, was also enhanced 12–72 h after PH, suggesting a potential positive effect of EPO on HC proliferation during rat liver regeneration. These data imply that the EPO receptor may allow EPO to promote HC proliferation through paths 3, 8, 12 and 14–17, mediating the RAS/MEK/ERK and PI3K/AκT pathways in rat liver regeneration after PH.

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