Key Laboratory for Cell Differentiation Regulation

Xinxiang, China

Key Laboratory for Cell Differentiation Regulation

Xinxiang, China

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Chang C.,Xinjiang University | Chang C.,Key Laboratory for Cell Differentiation Regulation | Xu C.,Key Laboratory for Cell Differentiation Regulation | Xu C.,Henan Normal University
International Journal of Biochemistry and Cell Biology | Year: 2010

To explore gene expression of aromatic amino acid family metabolism and their metabolic pathways of eight liver cell types in rat liver regeneration, eight kinds of rat regenerating liver cells were isolated by using the combination of percoll density gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect the expression changes of genes associated with aromatic amino acid family metabolism. The transcriptome atlas showed that the metabolic pathway of phenylalanine was mainly catalyzed into tyrosine in hepatic stellate cells in the initiation stage, tyrosine was oxidized into dopa and norepinephrine in biliary epithelia cells and dendritic cells, and norepinephrine was finally catalyzed into adrenaline in biliary epithelia cells and pit cells in the progress stage. Thyroid hormone of tyrosine catabolites was synthesized from tyrosine in almost all cells in different stage of LR, among which genes of T3 biosynthesis were increased in HCs, BECs, SECs and DCs in the progress stage. Tryptophan was decarboxylated to 5-hydroxytryptamine in dendritic cells in the progress stage. Based on the results as above, we concluded that phenylalanine is the major source of tyrosine, proliferation of biliary epithelia cells and dendritic cells maybe promote by tyrosine catabolites-dopa and norepinephrine, biliary epithelia cells and pit cells maybe promote by adrenaline. T3 maybe play a major role on proliferation of HCs, BECs, SECs and DCs in the progress stage. The proliferation of dendritic cells maybe promote by tryptophan catabolites-5-hydroxytryptamine. © 2010.


Chang C.,Xinjiang University | Chang C.,Key Laboratory for Cell Differentiation Regulation | Xu C.,Key Laboratory for Cell Differentiation Regulation | Xu C.,Henan Normal University
Cell Biology International | Year: 2010

To explore glutamine family amino acid metabolism of eight liver cell types in rat liver regeneration, eight kinds of rat regenerating liver cells were isolated by using the combination of Percoll density gradient centrifugation and immunomagnetic bead methods, then Rat Genome 230 2.0 Array was used to detect the expression profiles of the genes associated with metabolism of glutamine family amino acid in rat liver regeneration and finally how these genes involved in activities of eight regenerating liver cell types were analysed by the methods of bioinformatics and systems biology. The results showed that in the priming stage of liver regeneration, hepatic stellate cells and sinusoidal endothelial cells transformed proline and glutamine into glutamate; hepatocytes, hepatic stellate cells, sinusoidal endothelial cells and dendritic cells catabolized glutamate to 2-oxoglutarate or succinate; hepatic stellate cells and sinusoidal endothelial cells catalysed glutamate into glutamyl-tRNA for protein synthesis; urea cycle, which degraded from arginine, was enhanced in biliary epithelia cells, sinusoidal endothelial cells and dendritic cells; synthesis of polyamines from arginine was enhanced in biliary epithelia cells, sinusoidal endothelial cells, Kupffer cells and dendritic cells; the content of NO was increased in sinusoidal endothelial cells and dendritic cells; degradation of proline was enhanced in hepatocytes and biliary epithelia cells. In the progress stage, biliary epithelia cells converted glutamine into GMP and glucosamine 6-phosphate; oval cells converted glutamine into glucosamine 6-phosphate; hepatic stellate cells converted glutamine into NAD; the content of NO, which degraded from arginine, was increased in biliary epithelia cells, oval cells, pit cells and dendritic cells. In the termination stage, oval cells converted proline into glutamate; glutamate degradation, which degraded from arginine, was enhanced in hepatocytes and dendritic cells; the content of NO was increased in oval cells, sinusoidal endothelial cells, pit cells and dendritic cells. The synthesis of creatine phosphate was enhanced in hepatocytes, biliary epithelia cells, pit cells and dendritic cells in both progress and termination stages. In summary, glutamine family amino acid metabolism has some differences in liver regeneration in different liver cells. © The Author(s) Journal compilation © 2010 Portland Press Limited.


Chen X.G.,Henan University of Science and Technology | Xu C.S.,Key Laboratory for Cell Differentiation Regulation | Xu C.S.,Henan Normal University | Liu Y.M.,Henan University of Science and Technology
Genetics and Molecular Research | Year: 2013

It has been well established that ERK1/2 signaling, often subdivided into nine types of pathways, can regulate the hepatocyte proliferative response during liver regeneration. However, the effect of ERK1/2 signaling on the proliferation of other hepatic cell types remains unclear. We isolated and purified 8 liver cell types at 10 time points after 2/3 hepatectomy in adult rats. For each cell type, mRNA expression changes for ERK1/2 signaling-involved genes were monitored up to 168 h, using microarrays. Real-time PCR assays were performed for array data verification. The expression levels of these genes varied considerably between different cell types. Integrating microarray results with gene synergical analysis, at the priming phase, activation of integrin/Grb2/Ras pathway in hepatocytes apparently contributed to G0/G1 transition. Two other pathways, G-protein/EPAC/Rap1 and G-protein/PKA/Rap1, were stimulated in hepatic stellate cells, while RTK/PKC/Ras and RTK/Grb2/Ras were stimulated in Kupffer cells. At the progressive phase, the ERK1/2 pathway is involved in hepatocyte replication; three pathways, namely Ca2+/PKC/Ras, RTK/Grb2/Ras and G-protein/EPAC/Rap1, were found to play roles in biliary epithelial cell proliferation, while RTK/PKC/Ras and RTK/Grb2/Ras were involved in Kupffer cell proliferation, and G-protein/PKC/Ras in pit cell proliferation. At the terminal phase, the promotive effect of the ERK1/2 pathway on replication of hepatocytes, biliary epithelial cells, oval cells, hepatic stellate cells, Kupffer cells, and dendritic cells was considerably reduced, possibly due to their differentiation at the end of regeneration. G-protein/PKC/Ras, integrin/Grb2/Ras and G-protein/PKA/Rap1 pathways were active in sinusoidal endothelial cells, perhaps to aid in their proliferation. We conclude that ERK1/2 has a signaling role in the regulation of proliferation of 8 cell types during liver regeneration process. © FUNPEC-RP.


Wang G.,Henan Normal University | Xu C.,Henan Normal University | Xu C.,Key Laboratory for Cell Differentiation Regulation | Zhi J.,Henan Normal University | And 3 more authors.
Gene | Year: 2012

Rapid cell proliferation and growth occur in both liver cancer (LC) and liver regeneration (LR). Does it imply that LC and LR share some similar molecular mechanisms? To elucidate the intrinsic similarities and differences between the above two processes at transcriptional level, rat models of diethylnitrosamine-induced LC and 2/3 partial hepatectomy-induced LR were separately established. Then Rat Genome 230 2.0 Array was used to detect gene expression profiles of liver tissues obtained from the above two models, and bioinformatics methods, such as hierarchical clustering, k-means clustering and Expression Analysis Systematic Explorer (EASE), were applied to uncover the correlation between gene expression changes and physiological activities in LC and LR. Subsequently expression changes of six selected genes were confirmed by real-time quantitative RT-PCR. As a result, the expressions of 909 genes were found significantly changed during LC occurrence and 948 genes in LR. The expression profiles of the above two events were extremely different, and their expression patterns were classified into 6 clusters. Based on the correlation between expression patterns and functional profiles, we found that drug/toxin metabolism and oxidation reduction were induced in LC, but decreased in LR at the transcription level, while lipid, steroid and chemical homeostasis were remarkably repressed in LC but induced in LR; inflammation/immune response and apoptosis were not obvious or weaker in LC than in LR, whereas the activities of angiogenesis and cell adhesion/migration in LC were much stronger. © 2012 Elsevier B.V.


Xu C.,Henan Normal University | Xu C.,Key Laboratory for Cell Differentiation Regulation | Yang Y.,Henan Normal University | Yang Y.,Key Laboratory for Cell Differentiation Regulation | And 3 more authors.
Cellular and Molecular Biology Letters | Year: 2012

To 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. © 2012 © Versita Warsaw and Springer-Verlag Wien.


Wang G.-P.,Henan Normal University | Wang G.-P.,Key Laboratory for Cell Differentiation Regulation | Xu C.-S.,Henan Normal University | Xu C.-S.,Key Laboratory for Cell Differentiation Regulation
Molecular Biotechnology | Year: 2010

Liver regeneration (LR) is a process during which the liver recovers its mass and function after damage due to various causes such as partial hepatectomy (PH). It involves a sequence of well-orchestrated changes in physiological and biochemical activities, especially in the gene expression profile in a variety of liver cells. In order to produce reliable gene expression of target genes in eight kinds of rat hepatic cells during LR, the determination of internal control housekeeping genes (HKGs) is required. Eight kinds of hepatic cells were first isolated from liver tissue with high purity and activity. Then quantitative real-time reverse transcription (RT)-PCR was applied to detect expression changes of six commonly used HKGs (18SrRNA, B2M, ACTB, UBC, GAPDH, and HK1) in eight types of hepatic cells isolated from regenerating liver at 0, 2, 6, 12, 24, 30, 36, 72, 120, and 168 h after PH. The amplification of the HKGs was statistically analyzed by using geNorm algorithm. Using this method, 18SrRNA-UBC, ACTB-HK1, ACTB-GADPH, B2M-ACTB, 18SrRNA-UBC, B2M-UBC, B2M-ACTB, and B2M-UBC were found to be the two most stable reference genes for rat regenerating hepatocytes, hepatic stellate cells, Kupffer cells, biliary epithelial cells, sinusoidal endothelial cells, pit cells, dendritic cells, and oval cells, respectively, regardless of the stages of LR. In conclusion, this study has laid a good foundation for investigating gene expression of target genes in different types of hepatic cells during LR. © 2010 Springer Science+Business Media, LLC.


Xu C.,Henan Normal University | Xu C.,Key Laboratory for Cell Differentiation Regulation | Wang G.,Henan Normal University | Hao Y.,Henan Normal University | And 3 more authors.
Digestive Diseases and Sciences | Year: 2011

Background: Nonalcoholic fatty liver disease (NAFLD) is caused by fat metabolism disorders and thereby abnormal or excessive accumulation of fat in hepatocytes, and characterized by steatosis, inflammation, fibrosis, apoptosis or necrosis. Aim: This study was carried out to explore the correlation between gene expression profiles of rat livers and the occurrence and progression of NAFLD at the transcriptional level. Methods: A rat model of nonalcoholic steatohepatitis (NASH) was established by feeding male rats with high-fat emulsion via gavage, and Rat Genome 230 2.0 Array was used to detect gene expression profiles of liver tissues obtained from male rats following 0, 2, 4, and 6 weeks of high-fat emulsion feeding. Methods of bioinformatics and systems biology were applied to analyze the correlation between gene expression changes and physiological activities involved in NAFLD. Results: In total, 93 function-known genes, including 36 up-regulated and 57 down-regulated, differed significantly in expression compared to those of control rats, and 18 physiological activities were closely related to NAFLD. Especially, the activity of cell differentiation was decreased during the whole process of NAFLD, and the activities of inflammation response, stimulus response, cell migration and adhesion were attenuated in the second, fourth and sixth week, respectively. In the fourth and sixth weeks, lipid metabolism and cell apoptosis were augmented, and the former might be associated with the enhanced expression of plin, acsl6, scd2, elovl3, etc. Conclusion: These data provide useful information on the global gene expression changes due to high-fat emulsion feeding and bring important insights into the mechanisms of NAFLD. © 2011 Springer Science+Business Media, LLC.


Chen X.G.,Henan University of Science and Technology | Xu C.S.,Henan Normal University | Xu C.S.,Key Laboratory for Cell Differentiation Regulation
Genetics and Molecular Research | Year: 2014

Colony stimulating factors (CSF) have been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. However, it remains unclear about precise mechanism of action of CSF in regeneration at the cellular level. Therefore, eight rat liver cell types were isolated by Percoll gradient centrifugation and magnetic beads. CSF-mediated signaling pathway genes were obtained by searching the related pathway databases and their expression profiles in 8 hepatic cell types were measured using rat Genome 230 2.0 Microarray. RT-PCR was performed to assess the reliability of chip results. The result showed a large difference in expression profiles of CSF-mediated signaling pathway genes between different cell types; most genes involved in CSF-mediated signaling pathways were mainly unregulated across liver cell samples. The implication of these genes in LR was analyzed by the bioinformatics and systems biology method. According to chip results and gene synergy, a significant enhancement of the CSF3-mediated Pi3k/Akt pathway at 30-36 h in hepatocytes and at 24 h in biliary epithelial cells post-PH could be associated with active proliferation in these two cell types; the striking decrease in Jak/Stat cascade activity in hepatic stellate cells at 2 and 12 h post- PH or even inactive in dendritric cells during the whole LR implied that proliferation of these two cell types is possibly regulated by other signaling pathways. These data suggest the potential relevance of CSF in liver regeneration at the cellular level. © FUNPEC-RP.


Zhang J.,Henan Normal University | Zhang J.,Key Laboratory for Cell Differentiation Regulation | Ma C.,Henan Normal University | Ma C.,Key Laboratory for Cell Differentiation Regulation | And 7 more authors.
Gene | Year: 2014

Interleukin 18 (IL-18) is a proinflammatory cytokine with an ability to accelerate cell proliferation through activating other factors. However, little is yet understood of the role of IL-18 in the regulation of liver regeneration (LR). To study the effect of IL-18 on LR, the gene expression profiles of hepatocytes isolated from rat regenerative liver were determined by Rat Genome 230 2.0 microarray. Next, the synergistic effects of genes associated to IL-18 pathway were analyzed by expression profile function Et. Then, the expression level of IL-18 was examined by RT-PCR and ELISA. Finally, the effect of IL-18 on hepatocyte proliferation was detected by injecting recombinant rat IL-18 (rrIL-18) into rats immediately after partial hepatectomy (PH) and the rate of hepatocyte proliferation was detected by BrdU labeling. The microarray result showed that the expressions of 13 genes of IL-18 pathway and 49 cell proliferation genes regulated by the pathway were significantly altered at transcriptional level. The Et values of three branches of IL-18 pathway, NF-κB, p38 and JNK, were markedly enhanced during the priming and progressing phases of rat LR. The mRNA level of IL-18 was significantly elevated at 2 and 36. h, and its level in plasma was also significantly increased at 2. h, and reached the peaks at 12. h and 48. h after PH (p < 0.05). The number of BrdU positive cells was dramatically increased in rats treated with IL-18 compared to PBS control group (p < 0.01). In conclusion, IL-18 promotes rat hepatocyte proliferation in the LR priming and progressing phases after PH. © 2014 Elsevier B.V.


Wang G.-P.,Henan Normal University | Wang G.-P.,Key Laboratory for Cell Differentiation Regulation | Xu C.-S.,Henan Normal University | Xu C.-S.,Key Laboratory for Cell Differentiation Regulation
Genetics and Molecular Biology | Year: 2011

Rapidly proliferating tissue may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. Partial hepatectomy (PH) triggers cell proliferation during liver regeneration (LR). However, little is known on how DNA repair genes change and how they are regulated at the transcriptional level during LR. In the present study, the Rat Genome 230 2.0 array was used to detect the expression profiles of DNA repair genes during LR, and differential expression of selected genes was confirmed by real-time RT-PCR. 69 DNA repair genes were found to be associated with LR, more than half of which distributed in a cluster characterized by a gradual increase at 24-72h and then returning to normal. The expression of base excision repair- and transcription-coupled repair-related genes was enhanced in the early and intermediate phases of LR, whereas the expression of genes related to HR, NHEJ and DNA cross-link repair, as well as DNA polymerases and related accessory factors, and editing or processing nucleases, were mainly enhanced in the intermediate phase. The expression changes of genes in DNA damage response were complicated throughout the whole LR. Our data also suggest that the expression of most DNA repair genes may be regulated by the cell cycle during LR. © 2011, Sociedade Brasileira de Genética.

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