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Study on the activity of the signaling pathways regulating hepatocytes from G0 phase into G1 phase during rat liver regeneration

Abstract

Under normal physiological conditions, the majority of hepatocytes are in the functional state (G0 phase). After injury or liver partial hepatectomy (PH), hepatocytes are rapidly activated to divide. To understand the mechanism underlying hepatocyte G0/G1 transition during rat liver regeneration, we used the Rat Genome 230 2.0 Array to determine the expression changes of genes, then searched the GO and NCBI databases for genes associated with the G0/G1 transition, and QIAGEN and KEGG databases for the G0/G1 transition signaling pathways. We used expression profile function (E t ) to calculate the activity level of the known G0/G1 transition signal pathways, and Ingenuity Pathway Analysis 9.0 (IPA) to determine the interactions among these signaling pathways. The results of our study show that the activity of the signaling pathways of HGF, IL-10 mediated by p38MAPK, IL-6 mediated by STAT3, and JAK/STAT mediated by Ras/ERK and STAT3 are significantly increased during the priming phase (2–6 h after PH) of rat liver regeneration. This leads us to conclude that during rat liver regeneration, the HGF, IL-10, IL-6 and JAK/STAT signaling pathways play a major role in promoting hepatocyte G0/G1 transition in the regenerating liver.

Abbreviations

ERK:

extracellular regulated protein kinases

HGF:

hepatocyte growth factor

IL-6:

interleukin-6

IL-10:

interleukin-10

JAK:

Janus kinase

JNK:

c-Jun NH2-terminal kinase

MAPK:

mitogen-activated protein kinase

NF-κB:

nuclear factor κB

STAT3:

signal transducer and activator of transcription

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Correspondence to Cunshuan Xu.

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Li, M., Zhou, X., Mei, J. et al. Study on the activity of the signaling pathways regulating hepatocytes from G0 phase into G1 phase during rat liver regeneration. Cell Mol Biol Lett 19, 181–200 (2014). https://doi.org/10.2478/s11658-014-0188-2

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Keywords

  • Rat liver regeneration
  • Signal transduction
  • Hepatocyte G0/G1 transition
  • HGF
  • IL-10
  • IL-6
  • JAK/STAT
  • p38MAPK
  • Ras/ERK
  • STAT3
  • Ingenuity pathway analysis 9.0 (IPA)