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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 volume 19, pages 331–346 (2014)Cite this article

Abstract

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.

Abbreviations

Afp:

alpha-fetoprotein

ALB:

albumin

AκT:

v-Akt murine thymoma viral oncogene

Ctgf:

connective tissue growth factor

EPO:

erythropoietin

ERK:

extracellular regulated protein kinases

Fos:

FBJ osteosarcoma oncogene

G6P:

glucose-6-phosphatase

HCs:

hepatocytes

Hgf:

hepatocyte growth factor

Hif-2:

hypoxia-inducible factor-2

Il1rn:

interleukin 1 receptor antagonist

Jun:

jun protooncogen

MAPK:

mitogen-activated protein kinase

Med1:

mediator complex subunit 1

PH:

partial hepatectomy

PI3K:

phosphoinositide 3-kinase

Sirpa:

signal-regulatory protein alpha

Sox15:

SRY-box 15

SRY:

sex-determining region Y

TF:

transcription factor

TNF:

tumor necrosis factor

Vhlh:

von Hippel-Lindau syndrome homolog

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Authors and Affiliations

  1. College of Life Science, Henan Normal University, Xinxiang, 453007, P.R. China

    Jihong Zhang, Yajuan Yang, Tingting He, Yunqing Liu, Yun Zhou & Cunshuan Xu

  2. Key Laboratory for Cell Differentiation Regulation, Xinxiang, 453007, P.R. China

    Cunshuan Xu

  3. College of Life Science and Technology, Jinan University, Guangzhou, 510632, P.R. China

    Yongkang Chen

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  1. Jihong Zhang
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  2. Yajuan Yang
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  3. Tingting He
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Correspondence to Cunshuan Xu.

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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

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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