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Establishment of objective criteria for selecting relevant intestinal cell-based models

ABSTRACT: The objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30292 | GEO | 2012/06/24

SECONDARY ACCESSION(S): PRJNA143599

REPOSITORIES: GEO

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Establishment of objective criteria for selecting relevant intestinal cell-based models

Project description:The objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies. [Cell lines] Total RNA of biological replicate samples (i.e.different passages) from a panel of cell lines was collected and resulting amplified cRNA hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays. Samples are labeled as follows: SampleNumber_CellLine. [Laser dissected tumor cells (LDM)] Total RNA of three different samples laser dissected tumor cells, normal colonocytes, and enterocytes of ileum and two samples of jejunum was collected and resulting amplified cRNA hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays. Samples are labeled as follows: SampleNumber_TissueType_Origin.

2012-06-23 | E-GEOD-30292 | biostudies-arrayexpress

Particulate matter 10 exposure affects intestinal functionality in both inflamed 2D intestinal epithelial cell and 3D intestinal organoid models

Project description:A growing body of evidence suggests that particulate matter (PM10) enters the gastrointestinal (GI) tract directly, causing the GI epithelial cells to function less efficiently, leading to inflammation and an imbalance in the gut microbiome. PM10 may, however, act as an exacerbation factor in patients with inflamed intestinal epithelium, which is associated with inflammatory bowel disease. In this study, we established chronically inflamed intestinal epithelium models utilizing two-dimensional (2D) human intestinal epithelial cells (hIECs) and 3D human intestinal organoids (hIOs), which mimic in vivo cellular diversity and function, in order to examine the deleterious effects of PM10 in human intestine-like in vitro models. Inflamed 2D hIECs and 3D hIOs exhibited pathological features, such as inflammation, decreased intestinal markers, and defective epithelial barrier function. In addition, we found that PM10 exposure induced a more severe disturbance of peptide uptake in inflamed 2D hIECs and 3D hIOs than in control cells. This was due to the fact that it interferes with calcium signaling, protein digestion, and absorption pathways. The findings demonstrate that PM10-induced epithelial alterations contribute to the exacerbation of inflammatory disorders caused by the intestine. According to our findings, 2D hIEC and 3D hIO models could be powerful in vitro platforms for the evaluation of the causal relationship between PM exposure and abnormal human intestinal functions.

2023-07-19 | GSE227514 | GEO

The intestinal microbiota reprograms intestinal lipid metabolism through long non-coding RNA Snhg9

Project description:The intestinal microbiota is a key regulator of mammalian lipid absorption, metabolism, and storage. Here we show that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long non-coding RNA (lncRNA) Snhg9 in small intestinal epithelial cells. Snhg9 suppressed the activity of the transcription factor peroxisome proliferator–activated receptor γ (PPARγ) – a central regulator of lipid metabolism – by dissociating the PPARγ inhibitor Sirtuin 1 from cell cycle and apoptosis protein 2 (CCAR2). Forced expression of Snhg9 in the intestinal epithelium of conventional mice lowered dietary lipid absorption, reduced body fat, and protected against diet-induced obesity. The microbiota repressed Snhg9 expression through an immune cell signaling relay encompassing myeloid cells and innate lymphoid cells. Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.

2022-07-15 | GSE208020 | GEO

HuR promotes triglyceride synthesis and intestinal fat absorption

Project description:HuR promotes triglyceride synthesis and intestinal fat absorption

| PRJNA1093368 | ENA

HuR promotes triglyceride synthesis and intestinal fat absorption

Project description:HuR promotes triglyceride synthesis and intestinal fat absorption

| PRJNA1061476 | ENA

HuR promotes triglyceride synthesis and intestinal fat absorption

Project description:Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the mechanisms underlying are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3’UTR of Dgat2 mRNA and the introns 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3’UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

2024-01-10 | GSE252591 | GEO

HuR promotes triglyceride synthesis and intestinal fat absorption

2024-04-03 | GSE262777 | GEO

RNAseq of murine small intestinal tissue following epithelium-specific deletion of Bcl9/9l +/- Apc +/- mutant B-catenin

Project description:The aim of this experiment was to determine the contribution that components of the Wnt enhancesome (Bcl9/9l) make to Wnt driven intestinal transcriptional programmes in the context of normal intestinal homeostasis, or intestinal transformation driven by Apc depletion or B-catenin mutation.

2019-01-15 | E-MTAB-7546 | biostudies-arrayexpress

Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

Project description:Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity

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Reevaluation of Criteria and Establishment of Models for Total Thyroidectomy in Differentiated Thyroid Cancer.

Project description:IntroductionAfter the publication of the 2015 American Thyroid Association (ATA) guidelines, the indication for total thyroidectomy (TT) was reported to be underestimated before surgery, which may lead to a substantial rate of secondary completion thyroidectomy (CTx).Methods and materialsWe retrospectively analyzed differentiated thyroid cancer patients from Wuhan Union Hospital (WHUH). Univariate analysis was performed to evaluate all preoperative and intraoperative factors. New models were picked out by comminating and arranging all significant factors and were compared with ATA and National Comprehensive Cancer Network (NCCN) guidelines in the multicenter prospective Differentiated Thyroid Cancer in China (DTCC) cohort.ResultsA total of 5,331 patients from WHUH were included. Pre- and intraoperative criteria individually identified 906 (17.0%) and 213 (4.0%) patients eligible for TT. Among all factors, age <35 years old, clinical N1, and ultrasound reported local invasion had high positive predictive value to predict patients who should undergo TT. Accordingly, we established two new models that minorly revised ATA guidelines but performed much better. Model 1 replaced "nodule size >4 cm" with "age <35 years old" and achieved significant increase in the sensitivity (WHUH, 0.711 vs. 0.484; DTCC, 0.675 vs. 0.351). Model 2 simultaneously demands the presence of "nodule size >4 cm" and "age <35 years old," which had a significant increase in the specificity (WHUH, 0.905 vs. 0.818; DTCC, 0.729 vs. 0.643).ConclusionAll high-risk factors had limited predictive ability. Our model added young age as a new criterion for total thyroidectomy to get a higher diagnostic value than the guidelines.

| S-EPMC8458835 | biostudies-literature

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