- Short Communication
Expression profiles uncover the relationship between erythropoietin and cell proliferation in rat hepatocytes after a partial hepatectomy
Cellular & Molecular Biology Letters volume 19, pages 331–346 (2014)
Erythropoietin (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.
v-Akt murine thymoma viral oncogene
connective tissue growth factor
extracellular regulated protein kinases
FBJ osteosarcoma oncogene
hepatocyte growth factor
interleukin 1 receptor antagonist
mitogen-activated protein kinase
mediator complex subunit 1
signal-regulatory protein alpha
sex-determining region Y
tumor necrosis factor
von Hippel-Lindau syndrome homolog
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Zhang, J., Yang, Y., He, T. et al. Expression profiles uncover the relationship between erythropoietin and cell proliferation in rat hepatocytes after a partial hepatectomy. Cell Mol Biol Lett 19, 331–346 (2014). https://doi.org/10.2478/s11658-014-0198-0
- Rat liver regeneration
- Rat Genome 230 2.0 Microarray
- Gene expression profiles
- Gene synergetic effect