Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild type but not ILDR1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation is associated with increased [Ca2+]i consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.
Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion.
Specimen part
View SamplesTo characterize the effect of menthol on macrophages, comprehensive microarray analysis was performed in RAW 264.7 macrophage.
Menthol, a unique urinary volatile compound, is associated with chronic inflammation in interstitial cystitis.
Cell line, Treatment
View SamplesTo identify a cohort of rhythmically expressed genes in the murine Distal Colon,microarrays were used to measure gene expression over a 24-hour light/dark cycle.The rhythmic transcripts were classified according to expression patterns, functions and association with physiological and pathophysiological processes of the colon including motility, colorectal cancer formation and inflammatory bowel disease.
Transcriptional profiling of mRNA expression in the mouse distal colon.
No sample metadata fields
View SamplesThe goal of the study was to identify the genes which are regulated by Interleukin-2 in the CD4+ T cells of the scurfy mice during regulatory T-cell deficiency. Scurfy (Sf) mice bear a mutation in the forkhead box P3 (Foxp3) transcription factor, lack regulatory T-cells (Treg), develop multi-organ inflammation, and die prematurely. The major target organs affected are skin, lungs, and liver. Sf mice lacking the Il2 gene (Sf.Il2-/-), despite devoid of Treg, did not develop skin and lung inflammation, but the inflammation in liver, pancreas, submandibular gland and colon remained. Genome-wide microarray analysis revealed hundreds of genes were differentially regulated among Sf, Sf.Il2-/-, and B6 CD4+ T-cells but the most changes were those encoding receptors for trafficking/chemotaxis/retention and lymphokines. Our study suggests that IL-2 controls the skin and lung inflammation in Sf mice in an apparent "organ-specific" manner through two novel mechanisms: by regulating the expression of genes encoding receptors for T-cell trafficking/chemotaxis/retention and by regulating Th2 cell expansion and lymphokine production. Thus, IL-2 is a master regulator for multi-organ inflammation and an underlying etiological factor for various diseases associated with skin and lung inflammation.
IL-2-controlled expression of multiple T cell trafficking genes and Th2 cytokines in the regulatory T cell-deficient scurfy mice: implication to multiorgan inflammation and control of skin and lung inflammation.
Sex, Specimen part
View SamplesThe fidelity of sound transmission by cochlear implants in patients with sensorineural hearing loss could be greatly improved by increasing the number of frequency channels. This could be achieved by stimulating and guiding neurite outgrowth to reduce the distance between the implant's electrodes and the remnants of the spiral ganglion neurons. However, little is known about signaling pathways, besides those of neurotrophic factors, that are operational in the adult spiral ganglion. To systematically identify neuronal receptors for guidance cues in the adult cochlea, we conducted a genome-wide cDNA microarray screen with two-month-old CBA/CaJ mice. A meta-analysis of our data and those from older mice in two other studies revealed the presence of neuronal transmembrane receptors that represent all four established guidance pathwaysephrin, netrin, semaphorin, and slitin the mature cochlea as late as 15 months. In addition, we observed the expression of all known receptors for the Wnt morphogens, whose neuronal guidance function has only recently been recognized. In situ hybridizations located the mRNAs of the Wnt receptors frizzled 1, 4, 6, 9, and 10 specifically in adult spiral ganglion neurons. Finally, frizzled 9 protein was found in the growth cones of adult spiral ganglion neurons that were regenerating neurites in culture. We conclude from our results that adult spiral ganglion neurons are poised to respond to neurite damage, owing to the constitutive expression of a large and diverse collection of guidance receptors. Wnt signaling, in particular, emerges as a candidate pathway for guiding neurite outgrowth towards a cochlear implant after sensorineural hearing loss.
Expression of Wnt receptors in adult spiral ganglion neurons: frizzled 9 localization at growth cones of regenerating neurites.
Sex, Specimen part
View SamplesOver expression of MHC Class l protein in skeletal muscle causes myositis. Phenotype after expression in young mice is more severe.
Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis.
Sex, Specimen part, Treatment
View SamplesTo identify the precise molecular mechanisms that could contribute to the increase in colon carcinogenesis, microarray gene expression analysis was performed on colon RNA isolated from 5-week-old VhlF/F and VhlIE, VhlIE/Apcmin/+ and VhlF/F/Apcmin/+ mice.
Hypoxia-inducible factor-2α activation promotes colorectal cancer progression by dysregulating iron homeostasis.
Age, Specimen part
View SamplesTERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT.
TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.
No sample metadata fields
View SamplesComparative analysis can provide important insights into complex biological systems. As demonstrated in the accompanying paper, Translating Ribosome Affinity Purification (TRAP), permits comprehensive studies of translated mRNAs in genetically defined cell populations following physiological perturbations.
Application of a translational profiling approach for the comparative analysis of CNS cell types.
No sample metadata fields
View SamplesThe immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders. Hypocretin (orexin) containing neurons of the lateral hypothalamus are clearly essential for the normal regulation of sleep and wake behaviors, and have been implicated in feeding, anxiety, depression and reward. However, little is known about the molecular phenotypes of these cells, or the mechanism of their specification. We have generated a Hcrt bacTRAP line for comprehensive translational profiling of these neuronsin vivo. From this profile, we have identified 188 transcripts, as enriched in these neurons, in additions to thousands more moderately enriched or nominally expressed. We validated many of these at the RNA and protein level, including the transcription factor Lhx9. Lhx9 protein is found in a subset of these neurons, and ablation of these gene results in a 30% loss of Hcrt neuron number, and a profound hypersomnolence in mice.This data suggests that Lhx9 may be important for specification of some Hcrt neurons, and the subsets of these neurons may contribute to discrete sleep phenotypes.
Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation.
Sex, Specimen part
View Samples