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GSE21710
Mus musculus
4 Downloadable Samples
Description
Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis.
Publication Title
Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Inhibition of miR-33 results in increased cholesterol efflux and HDL-cholesterol levels in mice. In this study we examined the effect of miR-33 inhibition in a mouse model of atherosclerosis and observed significant reduction in atherosclerotic plaque size. At the end of the study, gene expression in macrophages from the atherosclerotic plaques was assessed.
Publication Title
Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3-UTR regulatory BAT (TGF activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts.
Publication Title
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The 24R,25-dihydroxyvitamin D metabolite (24R,25D) has long been suspected of participating to bone fracture repair. We used Cyp24a1-deficient mice, unable to produce 24R25D, to observe gene expression in callus tissue compared to that of control littermates.
Publication Title
Optimal bone fracture repair requires 24R,25-dihydroxyvitamin D3 and its effector molecule FAM57B2.
Sample Metadata Fields
Age, Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin
Publication Title
Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Tumor associated macrophages are contributing to local invasion, angiogensis, and metastasis during the progression of many kinds of tumor including glioma
Publication Title
Oligodendrocyte progenitor cells promote neovascularization in glioma by disrupting the blood-brain barrier.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
Publication Title
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel Foxo1-dependent transcriptional programs control T(reg) cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Analysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice
Publication Title
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI.
Publication Title
Essential role of pre-B-cell colony enhancing factor in ventilator-induced lung injury.
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