Altered gene expression in the small intestine of Mfge8 null and Cd36 null mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200320 | GEO | 2022/04/09
REPOSITORIES: GEO
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Project description:Altered gene expression in the small intestine of Mfge8 null and Cd36 null mice
| PRJNA824052 | ENA
Project description:BACKGROUND & AIMS: The scavenger receptor CD36 has versatile immuno-metabolic actions. CD36 is abundantly expressed in the small intestinal epithelium but its impact on gut homeostasis is unknown. METHODS: Wild type (WT) and CD36-null (CD36KO) mice were fed a chow diet and small intestinal morphology assessed by immunohistochemistry and electron microscopy (EM). Inflammation was evaluated from neutrophil infiltration, expression of cytokines and toll-like receptors. Barrier integrity was determined using FITC-dextran and circulating lipopolysaccharide (LPS). Enterocyte (Ent-CD36KO) and endothelial (EC-CD36KO) CD36 null mice were generated to test contribution of epithelial versus endothelial CD36 to the intestinal phenotype. RESULTS: The small intestine of CD36KO mice fed a chow diet showed abnormal remodeling of the extracellular matrix (ECM) with altered expression of ECM and junction proteins. Hypertrophy of cell junctions and basement membranes was observed by EM. The CD36KO intestines displayed neutrophil infiltration, inflammation and compromised barrier function. Systemic leukocytosis and neutrophilia were present in CD36KO mice and there was 80% reduction of anti-inflammatory Ly6Clow monocytes important for ECM regulation and tissue repair. Bone marrow transplants supported primary contribution of tissue injury in initiation of inflammation. Studies with Ent-CD36KO mice did not support a major contribution of enterocyte CD36 while endothelial CD36 deficiency associated with neutrophil infiltration, aberrant expression of tight junctions and inflammation in the small intestine. CONCLUSION: CD36 is important for maintenance of barrier function in the small intestine. CD36 deletion causes ECM remodeling with collagen accumulation, depletion of the Ly6Clow monocyte subset and chronic inflammation. Endothelial but not enterocyte CD36 loss is a significant contributor to the spontaneous inflammation.
2016-10-01 | GSE73569 | GEO
Project description:The NADPH-cytochrome P450 reductase (CPR) is essential for the functioning of microsomal cytochrome P450 (P450) monoxygenases. The biological functions of the CPR-dependent enzymes in the intestine are not known, despite the vast knowledge available on the biochemical properties of the various oxygenases. A mouse model with intestinal epithelium (IE)-specific Cpr-knockout (IE-Cpr-null) was recently generated in this laboratory (Zhang et al., Drug Metab. Dispos., 37, 651-657, 2009). The IE-Cpr-null mice did not display any obvious abnormalities in growth, development, or reproduction, and their intestines appeared to have a normal structure. Despite the absence of observable phenotypes, we hypothesized that loss of the enterocyte CPR expression will impact homeostasis of endogenous compounds, and expression of genes, that have critical biological function in the small intestine. In the present study, we have performed genomic analyses for enterocytes from IE-Cpr-null mice and their wild-type littermates, using Affymetrix Mouse Expression Set 430A 2.0 GeneChip Arrays. Our aim was to identify small intestinal gene-expression changes, which may shed light on potential biological roles of CPR and CPR-dependent enzymes in the small intestine. Our analysis revealed significant expression increases in P450s, transporters, cholesterol biosynthesis, and (unexpectedly) antigen presentation/processing. Further genomic and biochemical analyses revealed potential mechanisms linking CPR-dependent enzymes and the expression of major histocompatibility complex class II genes in the small intestine.
2012-04-11 | GSE35293 | GEO
Project description:The NADPH-cytochrome P450 reductase (CPR) is essential for the functioning of microsomal cytochrome P450 (P450) monoxygenases. The biological functions of the CPR-dependent enzymes in the intestine are not known, despite the vast knowledge available on the biochemical properties of the various oxygenases. A mouse model with intestinal epithelium (IE)-specific Cpr-knockout (IE-Cpr-null) was recently generated in this laboratory (Zhang et al., Drug Metab. Dispos., 37, 651-657, 2009). The IE-Cpr-null mice did not display any obvious abnormalities in growth, development, or reproduction, and their intestines appeared to have a normal structure. Despite the absence of observable phenotypes, we hypothesized that loss of the enterocyte CPR expression will impact homeostasis of endogenous compounds, and expression of genes, that have critical biological function in the small intestine. In the present study, we have performed genomic analyses for enterocytes from IE-Cpr-null mice and their wild-type littermates, using Affymetrix Mouse Expression Set 430A 2.0 GeneChip Arrays. Our aim was to identify small intestinal gene-expression changes, which may shed light on potential biological roles of CPR and CPR-dependent enzymes in the small intestine. Our analysis revealed significant expression increases in P450s, transporters, cholesterol biosynthesis, and (unexpectedly) antigen presentation/processing. Further genomic and biochemical analyses revealed potential mechanisms linking CPR-dependent enzymes and the expression of major histocompatibility complex class II genes in the small intestine. Adult (2.5-3.0 month-old) male IE-Cpr-null and WT litermates were used for all experiments. RNA was collected from eight mice of each genotype and RNA from two mice of the same genotype was pooled prior to hybridization to the microarray to create a total of four samples for each genotype.
2012-04-10 | E-GEOD-35293 | biostudies-arrayexpress
Project description:Despite the crucial function of the small intestine for nutrient uptake our understanding of the molecular events underlying the digestive function is very rudimentary. For example, it has only recently become evident that not all absorbed triacylglycerol (TAG) is immediately secreted in the form of chylomicrons (CM) by enterocytes. Instead, especially after high-fat challenges, parts of the re-synthesized TAG can be packaged into cytosolic lipid droplets (CLD) for transient storage in the endothelial layer of the small intestine. The reasons for this intermediate storage of TAGs are currently not completely understood. Several mechanisms, including alleviating lipotoxicity to enterocytes, limits in the rate of CM assembly or smoothening of the post-prandial peaks of blood hypertriglyceridemia have been suggested to explain this intermediate storage of TAG in CLD. Interestingly, rather than being evenly distributed across the small intestine, the proximal jejunum exhibits the highest TAG storage and CM secretion. Once stored in CLD, lipids are either remobilized in the inter-prandial phase or by various stimuli, e.g. a sequential meal containing either lipids or glucose. After remobilization, a triglyceride peak can be observed in the form of plasma CM well before lipids from the second meal have been digested in the intestinal lumen. To synthesize CM with lipids from CLD, CLD TAG have to be hydrolyzed to be transported across the ER membrane which can either be achieved by cytoplasmic TAG lipolysis or lipophagy. We hypothesize that correlating enzymatic activities of hydrolases with the reported distribution of TAG storage and chylomicron secretion in different sections of the small intestine is a promising strategy to pinpoint the key players in TAG remobilization. To rank hydrolases based on their relative activity in the different sections of the small intestine we have harnessed a serine hydrolase specific activity-based labeling strategy to label active hydrolases in freshly harvested enterocytes. Enrichment of activity labeled enzymes over control samples and abundance of enriched hydrolases from individual small intestine sections was analyzed using quantitative proteomics, resulting in a ranking of the most active hydrolases in 11 fractions of murine small intestine. Moreover, several clusters of enzymes showing similar activity distribution along the small intestine were identified.
2020-11-11 | PXD019593 | Pride
Project description:Adipose-derived MSCs (AMSC) are currently utilized in clinical trials for various diseases including osteoarthritis, amyotrophic lateral sclerosis, and multiple system atrophy. Whilst AMSCs may be defined by the surface expression of classical markers including CD44, CD90, CD105, and absence of CD45, these cells may exhbit donor-to-donor differences in differentiation potential. In this study we evaluated the expression of CD36 amongst AMSCs and utilized magnetic cell sorting to enrich for CD36+ cells. Whole transcriptome RNA-sequencing was performed on unsorted, CD36+ enriched, and CD36+ depleted cells to determine gene expression difference between these populations of cells. CD36 sorted or unsorted cells were then plated and maintained in growth medium. Cells were expanded for 2 passages and passage 8 cells were plated for RNA-sequencing analysis. Trizol reagent was used to harvest cells when they were proliferating cells (~80%) or 100% confluent cells.
2021-11-28 | GSE189525 | GEO
Project description:To investigate the role of cd36 on CD8 T cells,we did RNAseq to find the difference between CD36 ko and WT CD8 T Cells
2021-03-10 | GSE151160 | GEO
Project description:Monocytes and macrophages as components of innate immunity are critical for both homeostasis and inflammation. The scavenger receptor CD36, highly expressed in macrophages, promotes immunological responses mediated by recognition of molecular patterns on pathogens or endogenous ligands on apoptotic cells. CD36 mediated lipid uptake also allows metabolic adaptations that influence macrophage phenotype and polarization. CD36 binds diverse lipids including fatty acids and various lipoproteins, which could exert differential effects on macrophage conversion. Previous studies reported opposite outcomes due to CD36-mediated lipid uptake; macrophages converted to either an inflammatory or an alternatively activated phenotype. To determine the role of this receptor in vivo in the presence of physiological lipid sources, we created macrophage-specific CD36 knockout mice. Using zymosan-induced peritonitis to activate immune cells, we show through single cell RNA sequencing analysis that a broad variety of resident and infiltrated immune cells are present in the peritoneum 72h after the initial stimulus. CD36 deficiency did not affect the numbers of cells during the infiltration and resolution phases, but CD36 deficiency altered the macrophage transcriptome. Pathways related to innate immunity, antigen presentation and oxidative phosphorylation were upregulated in macrophages with CD36 deficiency, whereas those related to efferocytosis, adaptive immunity and B cell activation were downregulated. Despite these gene changes, neither immunoglobulin production nor peritoneal efferocytosis was altered by macrophage CD36 deficiency, nor were there changes in the numbers of circulating white blood cells. Thus, CD36 deficiency does not reduce the inflammatory phenotype of induced peritoneal macrophages.
2024-05-31 | GSE210795 | GEO
Project description:SV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used enterocytes from the mouse small intestine expressing TAg. Expression of TAg in the mouse intestine results in hyperplasia and dysplasia. Our analysis indicates that practically all gene expression regulated by TAg in enterocytes is dependent upon its binding and inactivation of the Rb-family proteins.
2009-09-01 | GSE16389 | GEO