Dissertation
Dissertation > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Liver metabolic disorders

Relationship and Significance of Gene Transcription Profiles in Rat Liver Regeneration and Non-Alcoholic Fatty Liver Disease Occurrence

Author HeChunXiao
Tutor XuCunShuan
School Henan Normal
Course Cell Biology
Keywords rat non-alcoholic fatty liver disease rat Liver regeneration Rat Genome 230 2.0 microarray JNK signaling pathway ERK1/2 signaling pathway
CLC R575.5
Type Master's thesis
Year 2011
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At present, the widely accepted view on the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is that NAFLD develops as a consequence of a "two-hit process". This study was to explore the correlation between gene expression profiles of rat livers and the occurrence of NAFLD, the similarities and differences between liver regeneration and the occurrence of NAFLD and the similarities and differences between the roles of JNK or ERK1/2 signaling pathway in liver regeneration and the occurrence of NAFLD at transcriptional level.Therefore, a rat model of NAFLD was established by feeding 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 SD rats following 2, 4, and 6 weeks of high-fat emulsion feeding, being used to detect gene expression profiles of liver tissues obtained from rats of high-fat emulsion feeding and rats under down PH and being used to detect the expression changes of gene being related to JNK or ERK1/2 signaling pathway in liver regeneration and the occurrence of NAFLD, and Quantitative real-time reverse transcription (RT)-PCR was used to test the validity of Rat Genome 230 2.0 microarray. Bioinformatics and systems biology methods were applied to analyze the correlation between gene expression changes of rat liver cells and the occurrence of NAFLD, showing that a total of 93 genes, were related to the occurrence of NAFLD, a total of 18 physiological activities, including responses to stimulus, inflammation and immune, signal transduction, transcription, transport, metabolisms of carbohydrate, lipid, amino acid and protein, homeostasis, cell proliferation, growth, differentiation and development, cellular organization, cell apoptosis, migration and adhesion were closely associated with and the occurrence of NAFLD. Of them, stimulus responses, inflammation response, cell differentiation and development, and cell migration and adhesion were dscreased in the occurrence of NAFLD, while lipid metabolisms were increased. Bioinformatics and systems biology methods were applied to analyze the correlation on gene expression profiles of liver tissues obtained from rats of high-fat emulsion feeding and rats under down PH, showing that 93 genes were changed significantly in expression in the occurrence of rat NAFLD and 948 genes in rat LR. Correlation of time was analyzed by H-clustering between the occurrence of rat NAFLD and LR. According to similarity of gene expression, a total of 1000 genes were divided into 4 kinds of groups by K-means. GO classifications and functional cluster analysis found that physiological activities including immune and inflammatory response, cell migration and adhesion, metabolisms of lipid and saccharides in the occurrence of NAFLD was weaker than those in LR, at the same time, metabolisms of lipid and saccharides were stronger than those in LR. In order to understand the similarities and differences of JNK, ERK1/2 signaling pathways in the occurrence of rat NAFLD and liver regeneration on the base of gene transcription, gene expression profiles were detected by Rat Genome 230 2.0 Array between them in this article, and physiological activities predicting in gene expression profiles were analyzed by bioinformatics and system biology. Analysis showed that JNK signaling pathway involved 42 paths, of them, 37 paths regulation cell proliferation and apoptosis of rat liver regeneration, but the effects on the occurrence of rat NAFLD is insignificant. 302 genes involved in JNK signaling pathway, Rat Genome 230 2.0 Array contains 240 genes, of them, 75 genes were changed significantly in expression, 64 genes were involved in LR and 21 genes were involved in the occurrence of rat NAFLD. ERK1/2 signaling pathway involved 14 paths, of them, 6 paths regulated cell proliferation of rat liver regeneration and the occurrence of NAFLD, but the effects on liver cirrhosis is insignificant. 165 genes involved in ERK1/2 signaling pathway, Rat Genome 230 2.0 Array contains 161 genes, of them, 46 genes were changed significantly in expression, 42 genes were involved in LR and 11 genes were involved in the occurrence of NAFLD.

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