ABSTRACT
Generally, extra-cellular-signal-regulated kinase 5 (ERK5) signaling pathway regulates many physiological activities, such as cell proliferation and cell differentiation. However, little is known about how ERK5 signaling pathway composed of 15 paths participates in regulating hepatocyte proliferation during liver regeneration (LR). In this study, to explore the influence ERK5 signaling pathway upon hepatocytes at gene transcription level, rat genome 230 2.0 array was used to detect expression changes of 75 related genes in isolated hepatocytes from rat regenerating liver. Bioinformatics and systems biology methods were applied to analyze the precise role of ERK5 signaling pathway in regulating hepatocyte proliferation during LR. Results showed that 62 genes were contained in the array and 22 genes were significantly changed. It was found that 6 paths were related to hepatocyte proliferation during rat LR. Among them, paths 3, 6 and 13 of ERK5 signaling pathway modulated cell cycle progression by decreasing the negative influence on ERK5 and paths 3, 4, 8 and 9 by reinforcing the positive influence on ERK5. In summary, the study shows that 22 genes and 6 paths of ERK5 signaling pathway participate in regulating proliferation of hepatocytes in rat LR.
Subject(s)
Animals , Cell Growth Processes/genetics , Cell Growth Processes/physiology , Gene Expression Profiling/methods , Hepatectomy , Hepatocytes/cytology , Hepatocytes/enzymology , Hepatocytes/physiology , Liver Regeneration/genetics , Liver Regeneration/physiology , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinase 7/genetics , Mitogen-Activated Protein Kinase 7/metabolism , Oligonucleotide Array Sequence Analysis/methods , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
Objective To investigate the possible contribution of PPAR-? coupled signaling pathways to rat liver regeneration (LR) at transcription level.Methods The above signaling pathways-related genes were obtained by collecting database data and retrieving pertinent literatures. The gene expression during LR was checked by Rat Genome 230 2.0 array, and LR-associated genes were identified by comparing difference between partial hepatectomy (PH) and operation control (OC) groups.Results Sixty four genes were found to be LR-associated. The number of initially and totally expressed genes occurring in initiation phase of LR, G0/G1 transition, cell proliferation, cell differentiation and structure-function reconstruction was 28, 4, 34, 2 and 72, 41, 247, 90 respectively. Classification of their expression patterns into 11 groups reflected diversity and complexity of gene expression alteration in LR. Conclusion PPAR-? coupled signaling pathways may promote glycogen synthesis in forepart, prophase and anaphase of LR, cell proliferation and migration in the whole LR, while inhibits inflammation during LR.
ABSTRACT
Objective To study the function of liver stem cells during at liver regeneration(LR) at transcriptional level.Methods The liver stem cell growth-and differentiation-related genes were obtained by data collection and literature review,and the gene expressions in rat regenerating liver were checked by Rat Genome 230 2.0 array.The relativity of the LR-associated genes was identified by comparing the discrepancy of gene expression changes between partial hepatectomy(PH) group and sham operation(SO) group.Results Fifty genes were found to be related with liver regeneration.The initial and total expressing gene numbers occurring in the initiation phase of liver regeneration(0.5-4 hours after PH),G_0/G_1 transition(4-6 hours after PH),cell proliferation(6-66 hours after PH),cell differentiation and structure-function reconstruction(72-168 hours after PH) were 24,10,21,2 and 24,23,46,26 respectively,indicating that the related genes were mainly triggered during the initiation phase,and worked at different phases.The total frequencies of their up-and down-regulation expression were 153 and 123 respectively,demonstrating that the expression of the major genes increased,and the minority decreased.Their expression profiles were classified into 6 types,indicating that the activities mentioned above were diverse and complicated during liver regeneration.Conclusion The growth and differentiation of liver stem cells are enhanced during liver regeneration.
ABSTRACT
Objective To investigate the actions of apoptotic pathways in rat liver regeneration(LR) at the transcription level.Methods The apoptosis genes were obtained by referring to the putative literatures and databases.Apoptotic-related genes expression profiles in rat LR were checked by Rat Genome 230 2.0 array.Identification of LR-associated genes was made by comparing the discrepancies of genes expression between partial hepatectomied(PH) and sham operatied(SO) rats.Results 252 genes were found to be related to liver regeneration.The initial and total expressing gene numbers occurring in the initiation phase of liver regeneration(0.5-4hours after PH),G_0/G_1 transition(4-6hours after PH),cell proliferation(6-66hours after PH),cell differentiation and structure-function reconstruction(72-168hours after PH) were 81,23,155,16 and 161,100,733,192 respectively.This demonstrated that LR-related genes primarily started their expression in the initiation phase,and worked in the different phases.The total times of their up-and down-regulated expression were 795 and 291,demonstrating that expression of most genes was enhanced in LR.Their expression patterns could be classified into 35 types,indicating the expressions of apoptosis-related genes in LR were diverse and complicated.Conclusion There are fifteen kinds of apoptosis pathways that associate to apoptosis regulation in the regenerating liver.
ABSTRACT
Objective To study the function of the genes regulating sex determination and differentiation during liver regeneration at transcriptional level.Methods The genes regulating sex determination and differentiation were obtained by referring to the theses and collecting the data of databases at NCBI,GENMAPP,KEGG,BIOCARTA and RGD,and their function and expression changes in rat liver regeneration were analysized by the Rat Genome 230 2.0 array.Results The initial and total expressed gene numbers in the starting phase of liver regeneration [half to four hours after partial hepatectomy(PH)],G_0/G_1 transition(4 to 6 hours after PH),cell proliferation 6 to 66 hours after PH),cell differentiation and tissue structural function reconstruction(72 to 160 hours after PH) were 41,6,18,3 and 41,25,57,41 respectively,which showed that the related genes were mainly triggered in the starting phase,and worked in different phases.Their expression similarity was classified into 5 groups:only up-,predominantly up-,only down-predominantly down-,up-/down-regulation,involving 22,9,15,9 and 7 genes respectively,and the total frequencies of their up-and down-regulation expressions were 231 and 146 respectively,demonstrating that the expression of the major genes was increased,and the minority decreased.Their expression time relevance was classified into 15 groups,showing that the cellular physiological and biochemical activities were phase related during liver regeneration.The gene expression patterns were classified into 20 types,indicating the diversity and complexity of the cellular physiological and biochemical activity.Conclusion The genes regulating male determination,male and female differentiation are enhanced mainly in the late early phase and prophase of liver regeneration,and the genes regulating female determination are enhanced mainly in the prophase.The function of the genes is closely related to liver regeneration.