Membrane estrogen receptor (ER) alpha stimulates AMP kinase to suppress SREBP1 processing and lipids in liver
Estrogen reduces lipid content in the liver exclusively from membrane receptor signaling.
Specimen part
View SamplesLectins are proteins present on cell surfaces or as shed extracellular proteins that function in innate immune defense as phagocytic receptors to recognize specific bacterial cell wall components. Based on the knowledge that cigarette smoking is associated with increased risk of bacterial infection, we hypothesized that cigarette smoking may modulate the expression of lectin genes in the airway epithelium. Affymetrix HG U133 Plus 2.0 microarrays were used to survey expression of lectin genes in large (3rd to 4th order bronchi) airway epithelium from 9 normal nonsmokers and 20 phenotypic normal smokers and small (10th to 12th order bronchi) airway epithelium from 13 normal nonsmokers and 20 phenotypic normal smokers. From the 72 lectin genes that were surveyed, there were no changes (>2-fold change, p<0.05) in gene expression in either large or small airway epithelium among normal smokers compared to nonsmokers except for a striking down regulation in both large and small airway epithelium of normal smokers of intelectin 1, a recently described lectin that participates in the innate immune response by recognizing and binding to galactofuranosyl residues in the cell walls of bacteria (large airway epithelium, p<0.003; small airway epithelium, p<0.002). TaqMan RT-PCR confirmed the observation that intelectin 1 was down-regulated in both large (p<0.05) and small airway epithelium (p<0.02) of normal smokers compared to normal nonsmokers. Immunohistochemistry assessment of biopsies of the large airway epithelium of normal nonsmokers demonstrated intelectin 1 was expressed in secretory cells, with qualitatively decreased expression in biopsies from normal smokers. Western analysis confirmed the decreased expression of intelectin 1 in airway epithelium of normal smokers compared to normal nonsmokers (p<0.02). Finally, compared to normal nonsmokers, intelectin 1 expression was decreased in small airway epithelium of smokers with early COPD (n= 13, p<0.001) and smokers with established COPD (n= 14, p<0.001), in a fashion similar to that of normal smokers. In the context that intelectin 1 is an epithelial molecule that likely plays a role in defense against bacteria, the down regulation of expression of intelectin 1 in response to cigarette smoking may contribute to the increase in susceptibility to infections observed in smokers, including those with COPD.
Decreased expression of intelectin 1 in the human airway epithelium of smokers compared to nonsmokers.
Sex, Age
View SamplesPurpose: To identify the changes in postnatal mouse conjunctival forniceal gene expression and their regulation by Klf4 around eye opening stage when the goblet cells first appear.
Mouse conjunctival forniceal gene expression during postnatal development and its regulation by Kruppel-like factor 4.
No sample metadata fields
View SamplesLocated in the perisinusoidal space of Disse, hepatic stellate cells (HSCs) communicate with all other liver cell types by physical association and / or by producing cytokines and chemokines. In liver disease and folllowing liver transplantation, elevated levels of endotoxin (bacterial lipopolysaccharide: LPS) stimulate HSCs to produce increased amounts of cytokines and chemokines. Transcriptomic analysis of cultured HSCs stimulated with LPS yields a survey of expression changes which potentially modulate the hepatic inflammatory and immune responses.
The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.
Sex, Specimen part
View SamplesIt is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex forming capacity promote exon inclusion. Destroying G-quadruplex forming capacity while keeping G-tracts intact abrogates exon inclusion. Analysis of RNA binding protein footprints revealed that G-quadruplexes are enriched in hnRNPF-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome. Moreover, hnRNPF regulates an EMT-associated CD44 isoform switch in a G-quadruplex-dependent manner, which results in inhibition of EMT. Mining breast cancer TCGA datasets, we demonstrate that hnRNPF negatively correlates with an EMT gene signature and positively correlates with patient survival. These data suggest a critical role for RNA G-quadruplexes in regulating alternative splicing. Modulation of G-quadruplex structural integrity may control cellular processes important for tumor progression. Overall design: PolyA-RNA-sequencing of two non-specific shRNA and two shhnRNPF HMLE cell lines
RNA G-quadruplex secondary structure promotes alternative splicing via the RNA-binding protein hnRNPF.
Specimen part, Cell line, Treatment, Subject
View SamplesPurpose: Klf5 plays a critical role in the mouse ocular surface (Kenchegowda et al., 2011. Dev Biol. 356:5-18). Here, we compare wild-type (WT) and Klf5-conditional null (Klf5CN) corneal gene expression at postnatal day-11 (PN11) and PN56 to identify the Klf5-target genes. Methods: Gene expression was compared using Affymetrix microarrays with QPCR validation. Transient transfection assays examined the effect of Klf5 on selected target gene promoter activities. Whole-mount corneal immunofluorescent staining examined neovascularization and CD45+ macrophage influx. Results: Expression of 714 and 753 genes was increased, and 299 and 210 genes decreased in PN11 and PN56 Klf5CN corneas, respectively, with 366 concordant increases, 72 concordant decreases and 3 discordant changes. Canonical pathway analysis identified 35 and 34 significantly (p<0.001) enriched pathways at PN11 and PN56, respectively, with 24 common pathways. PN56 Klf5CN corneas shared 327 increases and 91 decreases with the previously described Klf4CN corneas (Swamynathan et al., 2008. IOVS 49:3360-70). Angiogenesis and immune response-related genes were affected consistent with lymphangiogenesis and macrophage influx in Klf5CN corneas, respectively. Expression of 1574 genes was increased and 1915 decreased, in the WT PN56 compared with PN11 corneas. Expression of many collagens, matrix metalloproteinases and other extracellular matrix associated genes decreased in WT corneas between PN11 and PN56, while that of solute carrier family members increased. Conclusions: Differences in PN11 and PN56 corneal Klf5-target genes reveal dynamic changes in Klf5 functions during corneal maturation. Klf4- and Klf5-target genes do not overlap, consistent with their non-redundant roles in the mouse cornea.
Critical role of Klf5 in regulating gene expression during post-eyelid opening maturation of mouse corneas.
No sample metadata fields
View SamplesConditional disruption of Klf4 in the ectoderm-derived tissues of the eye results in defective cornea, conjunctiva and the lens.
Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4.
Specimen part
View SamplesIt is often overlooked that human ESCs are generated from in vitro cultured, often surplus/discard, embryos considered unsuitable for transfer in infertility clinics. In vitro culture of preimplantation embryos has been associated with a number of perturbations, including ultrastructure, gene expression, metabolism and post-transfer development. We report here the transcriptional profiles characteristic of ESC lines generated from either in vitro cultured or in vivo derived embryos.
Transcriptional differences between rhesus embryonic stem cells generated from in vitro and in vivo derived embryos.
Specimen part
View SamplesDendritic cells (DCs) regulate both innate and adaptive immune responses.
Early responding dendritic cells direct the local NK response to control herpes simplex virus 1 infection within the cornea.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
Sex, Age, Race
View Samples