Filters
Technology
Platform
GSE24031
Mus musculus
18 Downloadable Samples
Description
Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH. Research Design and Methods: C57Bl/6 mice were chronically fed a high fat diet to induce NAFLD and compared with mice fed low fat diet. Extensive histological and phenotypical analyses coupled with a time-course study of plasma proteins using multiplex assay was performed. Results: Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into 4 subgroups: LF-low (LFL) responders displaying normal liver morphology, LF-high (LFH) responders showing benign hepatic steatosis, HF-low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and HF-high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared to HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodelling. Plasma haptoglobin, IL-1, TIMP-1, adiponectin and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin and MIP-1 early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1, MIP-1 and MIP-2, whereas insulin, TIMP-1, GCP-2 and MPO emerged as late markers. Conclusions: Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH.
Publication Title
Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 59 Downloadable Samples
Description
Exposure to PFOA during gestation altered the expression of genes related to fatty acid catabolism in both the fetal liver and lung. In the fetal liver, the effects of PFOA were robust and also included genes associated with lipid transport, ketogenesis, glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis, steroid metabolism, bile acid biosynthesis, phospholipid metabolism, retinol metabolism, proteosome activation, and inflammation. These changes are consistent with activation of PPAR alpha. Non-PPAR alpha related changes were suggested as well.
Publication Title
Gene expression profiling in the lung and liver of PFOA-exposed mouse fetuses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
Description
Recent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2.
Publication Title
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Neuroprotective therapies for retinal degeneration may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1 in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration.
Publication Title
Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Better understanding alveolarization mechanisms could help improving prevention and treatment of diseases characterized by reduced alveolar number, especially bronchopulmonary dysplasia (BPD). Although signaling through fibroblast growth factor (FGF) receptors is essential for alveolarization, involved ligands are unidentified. FGF18 whose expression peaks during alveolar septation is likely to be involved. Herein, a mouse model of inducible, lung-targeted FGF18-transgene was used to advance the onset of FGF18 expression, and genome-wide expression changes were determined.
Publication Title
Profiling target genes of FGF18 in the postnatal mouse lung: possible relevance for alveolar development.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Notch3 is a transmembrane receptor which is critically important for the structure and myogenic response of distal arteries, particularly cerebral arteries. After activation of the receptor, the intracellular domain translocates in the nucleus to activate target genes transcription.
Publication Title
Transcriptome analysis for Notch3 target genes identifies Grip2 as a novel regulator of myogenic response in the cerebrovasculature.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
We have recently shown a remarkable regenerative capacity of the prenatal heart using a genetic model of mosaic mitochondrial dysfunction in mice. This model is based on inactivation of the X-linked gene encoding holocytochrome c synthase (Hccs) specifically in the developing heart. Loss of HCCS activity results in respiratory chain dysfunction, disturbed cardiomyocyte differentiation and reduced cell cycle activity. The Hccs gene is subjected to X chromosome inactivation, such that in females heterozygous for the heart conditional Hccs knockout approximately 50% of cardiac cells keep the defective X chromosome active and develop mitochondrial dysfunction while the other 50% remain healthy. During heart development, however, the contribution of HCCS deficient cells to the cardiac tissue decreases from 50% at midgestation to 10% at birth. This regeneration of the prenatal heart is mediated by increased proliferation of the healthy cardiac cell population, which compensate for the defective cells and allow the formation of a fully functional heart at birth. Here we performed microarray expression ananlyses on 13.5 dpc control and heterozygous Hccs knockout hearts to identify molecular mechanisms that drive embryonic heart regeneration.
Publication Title
Embryonic cardiomyocytes can orchestrate various cell protective mechanisms to survive mitochondrial stress.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Metastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here we addressed this question by using tumor cell lines derived from mice that develop metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. A feature of metastasis-prone tumor cells that distinguished them from metastasis-incompetent tumor cells was plasticity in response to changes in their microenvironment. They transited reversibly between epithelial and mesenchymal states, forming highly polarized epithelial spheres in 3-dimensional culture that underwent epithelial-mesenchymal transition (EMT) following treatment with transforming growth factor-beta or injection into syngeneic mice. This plasticity was entirely dependent upon the microRNA-200 family, which decreased during EMT. Forced expression of miR-200 abrogated the capacity of these tumor cells to undergo EMT, invade, and metastasize and conferred transcriptional features of metastasis-incompetent tumor cells. We conclude that microenvironmental cues direct tumor metastasis by regulating miR-200 expression.
Publication Title
Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The liver is frequently challenged by surgery-induced metabolic overload, viruses, or toxins, which induce the formation of reactive oxygen species. To determine the effect of oxidative stress on liver regeneration and to identify the underlying signalling pathways, we studied liver repair in mice lacking the Nrf2 transcription factor. In these animals, expression of several cytoprotective enzymes was reduced in hepatocytes, resulting in oxidative stress. As a consequence, tissue damage was aggravated, and liver regeneration after partial hepatectomy was delayed.
Publication Title
Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Tumor cells that give rise to metastatic disease are a primary cause of cancer-related death and have not been fully elucidated in patients with lung cancer. Here, we addressed this question by using tissues from a mouse that develops metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. We identified a metastasis-prone population of tumor cells that differed from those with low metastatic capacity on the basis of having sphere-forming capacity in Matrigel cultures, increased expression of CD133 and Notch ligands, and relatively low tumorigenicity in syngeneic mice. Knockdown of jagged1 or pharmacologic inhibition of its downstream mediator phosphatidylinositol 3-kinase abrogated the metastatic but not the tumorigenic activity of these cells. We conclude from these studies on a mouse model of lung adenocarcinoma that CD133 and Notch ligands mark a population of metastasis-prone tumor cells and that the efficacy of Notch inhibitors in metastasis prevention should be explored.
Publication Title
The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice.
Sample Metadata Fields
Specimen part
View Samples