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Expression Profiles And Action Analysis Of Growth Of Hepatic Cell-related Genes During Rat Liver Regeneration

Posted on:2009-07-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:L F ZhaoFull Text:PDF
GTID:1100360245488179Subject:Aquatic biology
Abstract/Summary:PDF Full Text Request
The liver has very strong capacity to regenerate. After rat partial hepatectomy, the remnant hepatocytes undergo orchestral physiological and biochemical activities, involving activation, proliferation, re-differentiation and structure-function reorganization, to compensate for the lost liver tissue, which lasts for about a week and is called liver regeneration (LR). The growth of various hepatic cells is a main biological event. So systematical studying on the expression profiles of hepatic cell growth-related genes as well as the physiological and biochemical activities it controls is an important aspect to elucidate the molecular mechanism of liver regeneration. Previous reports mainly studied the function of single gene or only a few genes in specific hepatic cell growth during liver regeneration, but the comprehensive function of the numerous genes associated with the growth of various hepatic cells was not reported. Hence this study obtained the genes participating in the growth of hepatic cells including liver stem cells, hepatocytes, biliary epithelial cells, Kupffer cells, hepatic endothelial cells, hepatic stellate cells, pit cells, dendritic cells and smooth muscle cells through searching for the data of NCBI, KEGG, RGD etc and referring to scientific articles, and detected their expression changes during rat liver regeneration by Rat Genome 230 2.0 chip which contained 28700 genes, ie, 90% genes of rat genome, and determined the standard of liver regeneration-associated genes. We used liver tissues at 23 time points after PH as experimental materials, and employed system biological and bioinformatic methods to study the expression patterns and the interactions of the genes mentioned above during liver regeneration. Meanwhile, the expression changes of four genes including g6pc, lifr, cd68 and npas2 were detected using fluorescence quantitative PCR to confirm the reliability of the Rat Genome 230 2.0 chip.Results showed that the expression tendency of these four randomly chosen genes obtained by the fluorescence quantitative PCR was basically consistent with that of chip detection; the dynamic expression analysis on these genes indicated that hepatic cell growth genes mainly started their expression at the initiation phase of liver regeneration and exerted their function at different periods. The expression of 53% genes was enhanced, 38% attenuated and 9% insignificantly changed. There were 42, 96, 88, 51, 62, 33, 52, 38 and 54 genes associated with liver regeneration among the genes participating in the growth of liver stem cells, hepatocytes, biliary epithelial cells, Kupffer cells, hepatic endothelial cells, hepatic stellate cells, pit cells, dendritic cells and smooth muscle cells, and they took on 5 expression trends, ie, only up-, predominant up-, only down-, predominant down-, and up-/down-regulation and presented 17, 29, 12, 19, 27, 23, 20, 9, 23 expression patterns, respectively. Except for hepatocytes, genes participating in other hepatic cell growth all exhibited four time relevance. The above-mentioned genes in sequence formed 103, 244, 211, 185, 144, 29, 98, 69 and 68 connectivities, and among them, myc, fos, mapk8, akt1, igfbp1 and crebbp had more connectivities.The above results demonstrate that the detection results of Rat Genome 230 2.0 chip have comparatively high reliability, and the research strategies and methods are effective to study the action of various hepatic cell growth-related genes during liver regeneration. The growth of liver stem cells, hepatocytes, biliary epithelial cells is enhanced mainly in the initiation and proliferation phase of liver regeneration; Kupffer cell, hepatic stellate cell, and smooth muscle cell growth is enhanced mainly in initiation phase and structure-function reconstruction phase; pit cell growth is enhanced mainly in proliferation phase; and hepatic endothelial cell growth is enhanced in the whole liver regeneration.
Keywords/Search Tags:Rat, Partial hepatectomy (PH), Rat genome 230 2.0 microarray, Growth of hepatic cells, Genes associated with liver regeneration
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