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Objective • To explore the effect of inhibiting transforming growth factor β (TGF-β) signaling pathway on the stem cell-mediated liver regeneration in mice after partial hepatectomy (PH). Methods • Eighteen C57BL/6 male mice were selected to establish the model of hepatectomy. mRNA and protein levels of the signal molecules in TGF-β pathway, as well as stem cell markers α-fetoprotein (AFP) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in the liver tissues were detected before (PH0) and on the 1st (PH1), 3rd (PH3) and 7th (PH7) day after operation. Then, additional 32 mice were assigned into inhibitor group [PH+SB-431542, 10 mg/(kg•d)] and control group (PH+normal saline). The mice were sacrificed on the 1st (PH1) and 3rd (PH3) day after operation and liver remnants were obtained. Realtime-PCR, Western blotting, and immunofluorescence staining were used to detect the expressing variation of TGF-β signaling pathway, AFP and LGR5. Results • The mRNA and protein expression of TGF-β1, phosphorylated SMAD2 (p-SMAD2) protein, Afp mRNA, the number of AFP immune-positive cells and Lgr5 mRNA were upregulated significantly after PH, peaked at PH3 (P<0.05) and recovered to pre-operative level at PH7. Compared with control group, the above indices were all obviously inhibited in inhibitor group at PH3 (P<0.05). Conclusion • TGF-β signaling pathway may regulate the stem cell-mediated liver regeneration in mice after PH.
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Objective To investigate the effect of neurolytic celiac plexus block (NCPB) on the inflammatory reaction of the remaining liver tissue and liver function after partial hepatectomy (PH) in rats.Methods Thirty male Sprague-Dawley rats of SPF were constructed as a PH model with deligation and ablation operated on their left and middle lobes,respectively.Then,they were randomly divided into two groups:NCPB group and control group.Twelve hours after the surgery,0.5％ lidocaine was given in the NCPB group once a day,while 0.9％ saline was given in the control group.Determination of liver function,generation of the remaining liver,and deposition of IL-β,TNF-α of the pathological section was respectively made on Day 1,3 and 7 after the surgery.Results On Day 1,3 and 7 after surgery,both the aspartate aminotransferase (AST) and the alanine aminotransferase (ALT) levels in NCPB group were,to different degrees,lower than those in the control group (P ＜ 0.05).Strikingly,total bilirubin in NCPB group was lower than that in control group (P ＜ 0.01) on Day 7,while the level of semm albumin was higher than that in control group (P ＜ 0.01).There was no statistically significant difference on the generation of the remaining livers between NCPB and control groups.On Day 3 and 7,the deposition of IL-β,TNF-α in the pathological sections of NCPB group were lower than those in control group.Conclusion NCPB can not only effectively reduce the damage of liver function caused by PH surgery,but also improve the inflammatory reaction of the residual liver.
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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.
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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.
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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.
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Objective To realize the expression changes and patterns of lipid metabolism and transport-related genes in rat liver regeneration(LR) at transcriptional level. Methods Genes involved in lipid metabolism and transport were obtained by retrieving the databases data and the related papers.The gene expression changes during LR was checked by Rat Genome 230 2.0 array,and LR-associated genes were identified by comparing gene expression difference between partial hepatectomy(PH) and sham operation(SO) groups. Results One hundred ninety three genes were found to be LR-associated.The number of initially and totally expressed genes occurring in forepart(0.5-4 hours after PH) of LR,prophase(6-12 hours after PH),metaphase(12-66 hours after PH),and anaphase(72-168 hours after PH) was 113,20,66,1 and 250,205,796,293,respectively.The number of their up-regulation and down-regulation was 852 and 630 times,and their expression profiles were classified into 27 types.The subdued transcription levels occur to the bile acid metabolism-involved genes in forepart and prophase of LR;the elevated transcription levels occur to the glucocorticoid catabolism-involved genes in forepart and anaphase;phospholipids synthesis-involved genes were up-regulated in prophase and metaphase,while phospholipids catabolism-involved genes were down-expressed;fatty acid,leukotriene and glycosphingolipid synthesis-involved genes,triglyceride and phosphatidylinositol metabolism-involved genes were up-regulated in metaphase,while glycosphingolipid catabolism-involved genes were down-expressed;the elevated transcription levels occur to the prostaglandin synthesis and fatty acid catabolism-involved genes in metaphase and anaphase;during almost the whole period of LR,genes participating in sex hormone,glucocorticoid and progesterone synthesis,sphingomyelin metabolism and lipid transport were up-regulated,while cholesterol metabolism-involved genes were down-expressed.Conclusion Lipid metabolism and transport during LR were diverse,and they were tightly related with LR.
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Objective To study the expression changes and profiles of nuclear structure and biogenesis-related genes in rat liver regeneration(LR). Methods Genes involved in nuclear structure and biogenesis were obtained by data collection and literature review.The gene expression changes during LR were checked by Rat Genome 230 2.0 array,and LR-related genes were identified by comparing gene expression difference between partial hepatectomy(PH) and sham operation(SO) groups.Results 406 genes were found to be LR-related.The numbers of initially and totally expressed genes occurring in the forepart(0.5-4 hours after PH) of LR,the prophase(6-12 hours after PH),the metaphase(12-66 hours after PH),and the anaphase(72-168 hours after PH) were 200,29,179,5 and 374,290,1?876,603,respectively.The numbers of their up-regulation and down-regulation were 1?224 and 496 times.The elevated transcription levels occur red to the nuclear organization and biogenesis-involved genes in the prophase and the metaphase of LR and to the nuclear membrane,nuclear matrix and nucleoplasm-involved genes in the metaphase;nuclear chromosome,nucleolus and nuclear functional protein complex-involved genes were up-regulated in the metaphase and the anaphase.Conclusion The expression of nuclear structure and biogenesis-related genes was active during LR,and it was tightly related with LR.
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Objective To study the regulating effect of in the regulation of cell surface receptor linked signal transduction pathway-related genes on rat liver regeneration(LR) at transcriptional level. Methods Genes involved in the above pathways were obtained by data collection and literature review.The gene expression changes during LR were checked by Rat Genome 230 2.0 array,and LR-related genes were identified by comparing gene expression difference between partial hepatectomy(PH) and sham operation(SO) groups. Results 491 genes were identified as LR-related.There were 742 kinds of interactive relations in 226 before-mentioned genes.In the 12 kinds of signaling pathways cytokine and chemokine mediated,enzyme linked receptor,G-protein coupled receptor,glutamate,antigen receptor-mediated,integrin-mediated,lipopolysaccharide-mediated, Notch,osmosensory,smoothened,Toll and Wnt——the numbers of up-regulated and down-regulated LR-related genes were 26 and 23,164 and 54,59 and 51,5 and 1,22 and 14,21 and 10,1 and 1,4 and 11,23 and 11, 32 and 17 respectively.In LR,the numbers of up-regulated and the down-regulated genes were 188 and 128,464 and 190,308 and 207,13 and 5,88 and 46,123 and 50,2 and 1,20 and 43,148 and 30,174 and 62 in the corresponding pathways.The genes which up regulated mainly occurred 0.5-16,30,42,54,96 hours and which down regulated mainly occurred 18-24,36,60-72,120-168 hours.Conclusion In liver regeneration,lipopolysaccharide-mediated and osmosensory signaling pathway have less effect,and the smoothened signaling pathway's role is attenuated,but the activities of the other 9 pathways are enhanced.
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Objective To study the expression changes and patterns of nucleic acid and their derivative metabolism,processing and transport-related genes in rat liver regeneration(LR) at transcriptional level. Methods The related genes were obtained by online data collection and literature review,and gene expression patterns in rat regenerated liver were checked by Rat Genome 230 2.0 array.LR-related genes were identified through the comparison of discrepancles in gene expression between partial hepatectomy(PH) and sham operation(SO) groups. Results 240 genes were determined to be related with liver regeneration.The number of initially expressive genes in the forepart of liver regeneration(0.5-4 hours after PH),prophase(6-12 hours after PH),metaphase(16-66 hours after PH),anaphase(72-168 hours after PH) were 65,14,150,11 respectively and the total expression numbers were 133,87,627,169 respeitirely.There were 6,5,22 and 9 expression patterns.Frequencies of up-regulation and down-regulation were 768 and 248.mRNA catabolism in prophase and metaphase,DNA recombination,modification and transcript,mRNA processing and transport in prophase,metaphase and anaphase,and nucleotides and their derivatives metabolism,as well as DNA replication,packaging and catabolism during the whole LR,were enhanced.Conclusion LR-related genes were mainly triggered in the forepart of liver regeneration,and funclioned at different phases.
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Objective To address the expression correlation of ribosome-related genes in rat regeneration liver(RL) and those in liver tumor at transcriptional level.Methods Genes involved in ribosome biogenesis,assembly and function,as well as their expression changes in liver tumor,were obtained by online data collection and literature review,and their expression profiles in rat regenerating liver were detected by Rat Genome 230 2.0 array.Expression similarities and differences of the above genes were analyzed using statistical methods. Results A total of 75 genes were found to be RL-related.In regenerated liver and liver tumor,the expressions of 18 genes increased and 6 genes decreased,and no significant expression changes were found in 51 genes in liver tumor.Conclusion The expression profiles of the ribosome-related genes in regenerated liver cells and liver tumor cells have both similarities and differences,and the former exhibit properties of more gradualness and complexity.