Expression profiles uncover the correlation of OPN signaling pathways with rat liver regeneration at cellular level

It has been documented that chemokines can positively regulate liver regeneration at the tissue level after partial hepatectomy. However, the precise mechanism of the effects of chemokines on regeneration at the cellular level remains poorly defined. In this study, 8 cell types from rat regenerating liver at 8 recovery time points after 2/3 hepatectomy were isolated and purified using Percoll density gradient centrifugation and immunomagnetic bead methods. The expression profiles of each cell type were monitored using a microarray. RT-PCR analysis was performed to validate the reliability of the microarray results. The results showed that, on the whole, the expression profiles of chemokine and receptor genes varied among different cell types; most genes involved in chemokine signaling pathways showed an increase in expression across the 8 liver cell types during liver regeneration. The implication of these genes in regeneration was analyzed by bioinformatics and systems biology methods. According to the microarray results and gene synergy, activation of chemokine signaling pathways at 24 h in biliary epithelial cells and at 2–12 h in dendritic cells may be triggered by CCL2–CCR2 and CCL7–CCR3, respectively; activation of Plc/Pkc and Pi3k/Akt pathways at 2–12 h in sinusoidal endothelial cells might be caused by CCL7–CCR1; and activation of the Src/Ptk, Src/Vav, and Plc/Pkc pathways at the priming stage may be related to the inductive effect of CCL7. These data suggest the potential relevance of the pro-inflammatory chemokines for liver regeneration at the cellular level.

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

Cellular & Molecular Biology Letters ◽

10.2478/s11658-014-0188-2 ◽

2014 ◽

Vol 19 (2) ◽

Cited By ~ 10

Author(s):

Menghua Li ◽

Xiaochun Zhou ◽

Jinxin Mei ◽

Xiaofang Geng ◽

Yun Zhou ◽

...

Keyword(s):

Liver Regeneration ◽

Signaling Pathways ◽

Rat Liver ◽

Activity Level ◽

Signal Pathways ◽

Profile Function ◽

Rat Liver Regeneration ◽

Priming Phase ◽

G0 Phase ◽

Rat Genome

AbstractUnder 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.

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Expression profiles of the genes associated with metabolism and transport of amino acids and their derivatives in rat liver regeneration

Amino Acids ◽

10.1007/s00726-007-0576-2 ◽

2007 ◽

Vol 34 (1) ◽

pp. 91-102 ◽

Cited By ~ 21

Author(s):

C. S. Xu ◽

C. F. Chang

Keyword(s):

Amino Acids ◽

Liver Regeneration ◽

Rat Liver ◽

Expression Profiles ◽

Rat Liver Regeneration

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Expression profiles of the apoptosis signaling pathway mediated by death receptor and endoplasmic reticulum in rat liver regeneration

Genetics and Molecular Research ◽

10.4238/gmr.15028288 ◽

2016 ◽

Vol 15 (2) ◽

Author(s):

X.K. Xing ◽

M.H. Li ◽

X.S. Zhu ◽

C.S. Xu

Keyword(s):

Endoplasmic Reticulum ◽

Liver Regeneration ◽

Signaling Pathway ◽

Rat Liver ◽

Expression Profiles ◽

Death Receptor ◽

Rat Liver Regeneration

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Study on correlation of signal molecule genes and their receptor-associated genes with rat liver regeneration

Genome ◽

10.1139/g09-022 ◽

2009 ◽

Vol 52 (6) ◽

pp. 505-523 ◽

Cited By ~ 4

Author(s):

Cun-Shuan Xu ◽

Heng-Yi Shao ◽

Bin Du

Keyword(s):

Gene Expression ◽

Liver Regeneration ◽

Rat Liver ◽

Expression Profiles ◽

Expression Patterns ◽

Signal Molecules ◽

Transcriptional Level ◽

Scientific Publications ◽

Signal Molecule ◽

Rat Liver Regeneration

To investigate the effect of signal molecules and their receptor-associated genes on rat liver regeneration (LR) at the transcriptional level, the associated genes were originally obtained by retrieving the databases and related scientific publications; their expression profiles in rat LR were then checked using the Rat Genome 230 2.0 microarray. The LR-associated genes were identified by comparing gene expression difference between partial hepatectomy groups and operation-control groups. A total of 454 genes were proved to be LR related. The genes associated with the seven kinds of signal molecules (steroid hormones, fatty acid derivatives, protein and polypeptide hormones, amino acids and their derivatives, choline, cytokines, and gas signal molecules) were detected to be enriched in a cluster characterized by upregulated expression in LR. The number of genes related to the seven kinds of signal molecules was, in sequence, 63, 27, 100, 102, 16, 166, and 18. The 1027 frequencies of upregulation and 823 frequencies of downregulation in total as well as 42 types of different expression patterns suggest the complex and diverse gene expression changes in LR. It is presumed that signal molecules played an important role in metabolism, inflammation, cell proliferation, growth and differentiation, etc., during rat LR.

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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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