MUTYH is associated with hepatocarcinogenesis in a NASH model mouse
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE157142 | GEO | 2020/08/31
REPOSITORIES: GEO
Similar Datasets
Project description:MUTYH is associated with hepatocarcinogenesis in a NASH model mouse
| PRJNA660256 | ENA
Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s. A total of 4 wild-type mice were administered a standard diet (STD; control group) and 4 wild-type mice were administered a HFHC diet (HFHC).
2014-01-03 | E-GEOD-53381 | biostudies-arrayexpress
Project description:In murine NAFL/NASH models, high-fat high-calorie fructose (HFHC) diet fed for 16 weeks induces hepatic steatosis, inflammatory cells infilatration and early stage fibrosis. In addition, HFHC diet 16 weeks but not 8 weeks is accompanied with weight gain and insulin resistance. The aim of this study is to determine the gene expression changes in mouse liver by HFHC diet for 8weeks.
2021-12-08 | GSE154426 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is most prevalent form of liver disease, affecting over 30% of Americans. Perfluoroalkyl substances (PFAS) represent a family of environmental toxicants that have infiltrated the living world. This study explores diet-PFAS interactions and their potential role in the increasing global incidence of NAFLD. Male C57BL/6 mice were fed with either a low-fat diet (11% kcal from fat) or a high fat (58% kcal from fat) high carbohydrate (42g/L) diet with or without PFOS or PFHxS in feed (0.0003% w/w) for 29 weeks. Proteomic, lipidomic, and gene expression measurement techniques were utilized to explore mechanistic pathways. With administration of a high fat high carbohydrate (HFHC) diet, PFOS and PFHxS augmented macrovesicular steatosis, indicative of fatty liver. There was a clear shift in the lipidome of the serum phosphatidylcholines, phosphatidylethanolamines, and triglycerides with PFAS exposure. Finally, chain length exerted significant influence on tissue partitioning and the resulting hepatic gene and protein signatures of PFHxS and PFOS in vivo.
2020-09-15 | PXD015976 | Pride
Project description:Studying whether removal of base-excision repair from mitochondria will result into increase in mitochondrial DNA (mtDNA) mutation load. The endogenous genes of OGG1 and MUTYH DNA glycosylases were modified to lack the genomic region encoding for the predicted mitochondrial targeting sequence. The mouse lines used: A mouse line that lacks the region encoding for the mitochondrial targeting sequence (L2 to W23) of OGG1 (Ogg1 dMTS mice). A mouse line that lacks the region encoding the mitochondrial targeting sequence (K2 to P33) of MUTYH (Mutyh dMTS mice). To accumulate mutations to the mitochondrial DNA these mice were bred double homozygous Mutyh dMTS x Ogg1 dMTS mice as a maternal lineage for five consecutive generations and mitochondrial DNA from liver was extracted from the offspring and sequenced with Illumina. OGG1 and MUTYH are involved in repair of 8-oxo-dG from DNA. 8-oxo-dG can be a mutagenic lesion because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
2018-07-13 | E-MTAB-6532 | biostudies-arrayexpress
Project description:Previous studies have identified liver cancer associated to NASH, diabetes, obesity, and some genetic risk factors. We want to investigate the synergism between diet and genetic risk factors in hepatocarcinogenesis using omics data of four background zebrafish in three types of diet. We found the fishes have more genetic risk factors at the same time, and have higher probability to accelerate cancer formation. Overfed and high fat diet will increase the chance. Moreover, the results showed metabolism and genetic information processing, including the pathways of fatty acid metabolism, steroid biosynthesis and ribosome biogenesis are highly affected in hepatocellular carcinoma.
2019-07-19 | GSE134494 | GEO
Project description:Previous studies have identified liver cancer associated to NASH, diabetes, obesity, and some genetic risk factors. We want to investigate the synergism between diet and genetic risk factors in hepatocarcinogenesis using omics data of four background zebrafish in three types of diet. We found the fishes have more genetic risk factors at the same time, and have higher probability to accelerate cancer formation. Overfed and high fat diet will increase the chance. Moreover, the results showed metabolism and genetic information processing, including the pathways of fatty acid metabolism, steroid biosynthesis and ribosome biogenesis are highly affected in hepatocellular carcinoma.
2019-07-19 | GSE134495 | GEO
Project description:Oxidative stress is a major risk factor for Alzheimer’s disease (AD), which is characterized by brain atrophy, amyloid plaques, neurofibrillary tangles, and loss of neurons. 8-Oxoguanine, a major oxidatively generated nucleobase highly accumulated in the AD brain, is known to cause neurodegeneration. In mammalian cells, several enzymes play essential roles in minimizing the 8-oxoguanine accumulation in DNA. MUTYH with adenine DNA glycosylase activity excises adenine inserted opposite 8-oxoguanine in DNA. MUTYH is reported to actively contribute to the neurodegenerative process in Parkinson and Huntington diseases and some mouse models of neurodegenerative diseases by accelerating neuronal dysfunction and microgliosis under oxidative conditions; however, whether or not MUTYH is involved in AD pathogenesis remains unclear. In the present study, we examined the contribution of MUTYH to the AD pathogenesis. Using postmortem human brains, we showed that various types of MUTYH transcripts and proteins are expressed in most hippocampal neurons and glia in both non-AD and AD brains. We further introduced MUTYH deficiency into AppNL-G-F/NL-G-F knock-in AD model mice, which produce humanized toxic amyloid-β without the overexpression of APP protein, and investigated the effects of MUTYH deficiency on the behavior, pathology, gene expression, and neurogenesis. MUTYH deficiency improved memory impairment in AppNL-G-F/NL-G-F mice, accompanied by reduced microgliosis. Gene expression profiling strongly suggested that MUTYH is involved in the microglial response pathways under AD pathology and contributes to the phagocytic activity of disease-associated microglia. We also found that MUTYH deficiency ameliorates impaired neurogenesis in the hippocampus, thus improving memory impairment. In conclusion, we propose that MUTYH, which is expressed in the hippocampus of AD patients as well as non-AD subjects, actively contributes to memory impairment by inducing microgliosis with poor neurogenesis in the preclinical AD phase and that MUTYH is a novel therapeutic target for AD, as its deficiency is highly beneficial for ameliorating AD pathogenesis.
2021-12-23 | GSE157766 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of hepatic disease and feeding mice a High-Fat, High-Caloric (HFHC) diet is a standard model of NAFLD. In order to better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. 265 (A/J × C57BL/6J) F2 male mice were fed a HFHC diet for 8 weeks. QTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1 and Socs3 on Chr 1 (164.0-185.4 Mb and 174.4-190.5 Mb, respectively) and Chr 11 (41.1-73.1 Mb and 44.0-68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9-117.4 Mb). C57BL/6J-Chr 11A/J/ NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (p<0.05), while C57BL/6J-Chr 1A/J/ NaJ mice retained the C57BL/6 phenotype. In addition, we replicated the eQTLs on Chr 1 and 12 (LOD scores ? 3.5) using mice from the BXD murine reference panel challenged with CCl4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3 on Chr 1 and 11, and consomic mice confirmed that replacing the C57BL/6 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases. Liver samples from eight-week-old AJ and C57BL6J males fed a High Fat High Calorie diet.
2014-08-02 | E-GEOD-56987 | biostudies-arrayexpress
Project description:To explore key features associated with the resolution process in liver fibrosis, we here applied a unique murine model, in which mice were fed HFHC diet for 24 weeks, and then continued with the HFHC diet (HFHC) or switched to a normal diet (RES) for 5 weeks. We noted that both the frequency and number of intrahepatic CD8+ T cells remained significantly high in RES mice compared to normal diet-fed mice (ND). To reveal the transcriptome profiling-based subtypes of CD8+T cells present during the liver fibosis resolution, we performed scRNA-seq analysis. Total of 25851 cells were clustered into 17 clusters based on the gene signatures. We revealed CD69+CD103-CD8+ Trm cell enrichment in fibrosis resolution livers. scTCR-seq analysis further revealed the clonal enrichment mainly in the Cd44+Sell-S1pr1- liver Trm fractions. In addition, TCR clonotypes enriched in liver CD8+ Trm cells of RES mice were expanded compared to those in liver CD8+ T cells of ND mice, and rarely detected in spleen CD8+ T cells.
2021-06-11 | GSE176210 | GEO