Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA135013 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Growth hormone signaling in hepatocytes is fundamentally important. Disruptions in this pathway have led to fatty liver and other metabolic abnormalities. Growth hormone signals through the JAK2/STAT5 pathway. Mice with hepatocyte specific deletion of STAT5 were previously shown to develop fatty liver. Our aim in this study was to determine the effect of deleting JAK2 in hepatocytes on liver gene expression. To do so, we generated animals with hepatocyte specific deletion of JAK2. Hepatocyte-specific JAK2-deficient mice (JAK2L) were generated by mating floxed JAK2 mice (in a mixed (C57Bl/6:129Sv) background) to mice carrying an Alb promoter-regulated Cre transgene on a 100% C57Bl/6 background purchased from the Jackson Labs. Livers were harvested from 8 week old animals for RNA extraction and hybridization.
2011-04-30 | E-GEOD-26188 | biostudies-arrayexpress
Project description:Growth hormone signaling in hepatocytes is fundamentally important. Disruptions in this pathway have led to fatty liver and other metabolic abnormalities. Growth hormone signals through the JAK2/STAT5 pathway. Mice with hepatocyte specific deletion of STAT5 were previously shown to develop fatty liver. Our aim in this study was to determine the effect of deleting JAK2 in hepatocytes on liver gene expression. To do so, we generated animals with hepatocyte specific deletion of JAK2.
2011-05-01 | GSE26188 | GEO
Project description:Impairment of hepatic growth hormone (GH)- janus kinase (JAK) 2- signal transducer and activator of transcription (STAT) 5 signaling is associated with non-alcoholic fatty liver disease, while persistently high levels of GH can result in hepatic inflammation and liver cancer. Despite its anti-steatotic functions, STAT5 in hepatocytes has been implicated to be a tumor suppressor, whose loss strongly accelerates tumor formation in the presence of high GH levels. Yet, it remains unclear whether the upstream kinase JAK2 exerts similar tumor-suppressive functions. To address this question, we crossed a mouse model of inflammatory liver cancer (GHtg) to mice harboring the hepatocyte-specific deletion of JAK2 (JAK2Îhep) and compared them to GHtgSTAT5Îhep mice. We show that JAK2 deficiency in the GHtg background resulted in profound steatosis at young age due to ectopic lipid redistribution and increased hepatic de novo lipogenesis. Generation of reactive oxygen species (ROS) was increased in all genotypes compared to wildtype controls, while DNA damage and lipid peroxidation were observed only in GHtg and GHtgSTAT5Îhep animals. Importantly, Affymetrix analysis revealed that the expression of glutathione S-transferases (GSTs), a major group of detoxification enzymes, was strongly upregulated in JAK2 deficient livers. In vitro and in vivo studies further confirmed that ruxolitinib-mediated inhibition of JAK2 led to significant upregulation of GSTs, indicating a direct involvement of JAK2 in the negative regulation of these genes. Strikingly, despite equally profound hepatosteatosis and ROS production as in GHtgSTAT5Îhep mice, loss of JAK2 significantly delayed tumor formation in GHtg mice. Conclusion: Thus, in absence of hepatic JAK2, mice were protected against elevated ROS-induced DNA damage and lipid peroxidation through significant expression of GSTs.
2016-10-01 | E-MTAB-3774 | biostudies-arrayexpress
Project description:RNA-sequencing of hepatocyte specific ABCA1 deletion mice
| PRJNA378792 | ENA
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
2010-01-27 | GSE17644 | GEO
Project description:Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism
| PRJNA111907 | ENA
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2021-05-05 | PXD022309 | Pride
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2018-04-24 | PXD007288 | Pride
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Liver fibrosis model of hepatocyte-specific FOXA2 knockout mice
| PRJNA381475 | ENA