Global transcriptional analysis of human FHs 74 Int intestinal epithelial cells after exposure to advanced glycation end products
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PROVIDER: PRJNA1201118 | ENA |
REPOSITORIES: ENA
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Project description:Advanced glycation end products (AGEs) are formed during the thermal processing of food and have been implicated in the pathogenesis of a series of chronic inflammatory diseases. AGEs are hypothesized to interact with the intestinal epithelium upon the ingestion of thermally processed food, however, their direct effect on intestinal epithelial cells is poorly understood. This study investigates transcriptomic changes in human intestinal epithelial FHs 74 Int cells after exposure to methylglyoxal-modified human serum protein (AGE-HS), S100A12, a known RAGE ligand, and unmodified human serum proteins (HS) in comparison to PBS treated cells. Surprisingly, AGE-HS treatment did not result in significant differential gene expression at standard analysis thresholds, while unmodified HS induced minor transcriptional changes. S100A12 also elicited no significant gene expression alterations. However, GSEA revealed subtle but coordinated changes – AGE-HS treatment induced downregulation of gene sets linked to MYC, interferon responses, and oxidative phosphorylation, paralleling some effects observed with S100A12. Also, KEGG pathway analysis revealed partial overlap between responses to AGE-HS and S100A12 affecting pathways associated with oxidative phosphorylation and neurodegenerative diseases such as Alzheimer, Parkinson, and Huntington disease. This study provides the first global transcriptomic analysis of intestinal epithelial cells treated with AGE-modified proteins. The effects were less pronounced than expected, thus, these data challenge previous reports of robust AGE-induced inflammatory and proliferative effects and emphasize the importance of rigorous endotoxin testing and the use of appropriate controls.
2025-09-16 | GSE285048 | GEO
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM).
2016-02-16 | GSE65952 | GEO
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM). mRNA profiles of Primary human posterior longitudinal ligament cells stimulated with various stimuli (Control, 1µM AGE-BSA, 5µM AGE-BSA, 1µM AGE-BSA with BMP2, 5µM AGE-BSA with BMP2) were generated by deep sequencing on Ion Proton
2016-02-16 | E-GEOD-65952 | biostudies-arrayexpress
Project description:Cryptosporidium parvum is an important opportunistic parasite pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Certain parasite molecules can be delivered into host epithelial cells and may act as effector molecules for parasite intracellular development. This study aims to measure the impact of transfection of a parasite low-protein coding potential RNA transcript, Cdg7_FLc_0990, on the transcriptome profile in intestinal epithelial cells. Human intestinal epithelial INT (FHs 74 Int) cells were grown to 80% confluence and transfected with the Cdg7_FLc_0990 full-length or the empty vector for 48h. Total RNA was collected for the genome-wide analysis. RNA from INT cells following C. parvum infection for 48h and from cell of the non-infected control was also collected for the analysis. The Agilent SurePrint G3 Human Gene Expression Microarray (G4851B) was used for the genome-wide analysis, which provides full coverage of genes and transcripts with the most up-to-date content, including mRNAs and lincRNAs (http://www.chem.agilent.com/store/en_US/Prod-G4851B/G4851B)
2017-08-22 | GSE87047 | GEO
Project description:Cryptosporidium parvum is an important opportunistic parasite pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Certain parasite molecules can be delivered into host epithelial cells and may act as effector molecules for parasite intracellular development. This study aims to measure the impact of transfection of two parasite low-protein coding potential RNA transcripts, cdg2_FLc_0220 and cdg7_FLc_1000, on the transcriptome profile in intestinal epithelial cells. Human intestinal epithelial INT (FHs 74 Int) cells were grown to 80% confluence and transfected with the cdg2_FLc_0220 or cdg7_FLc_1000full-length or the empty vector for 48h. Total RNA was collected for the genome-wide analysis. The Agilent SurePrint G3 Human Gene Expression Microarray (G4851B) was used for the genome-wide analysis, which provides full coverage of genes and transcripts with the most up-to-date content, including mRNAs and lincRNAs (http://www.chem.agilent.com/store/en_US/Prod-G4851B/G4851B).
2018-02-21 | GSE94128 | GEO
Project description:BackgroundDrinking water disinfection inadvertently leads to the formation of numerous disinfection by-products (DBPs), some of which are cytotoxic, mutagenic, genotoxic, teratogenic, and potential carcinogens both in vitro and in vivo.ObjectivesWe investigated alterations to global gene expression (GE) in nontransformed human small intestine epithelial cells (FHs 74 Int) after exposure to six brominated and two chlorinated DBPs: bromoacetic acid (BAA), bromoacetonitrile (BAN), 2,6-dibromo-p-benzoquinone (DBBQ), bromoacetamide (BAM), tribromoacetaldehyde (TBAL), bromate (BrO3-), trichloroacetic acid (TCAA), and trichloroacetaldehyde (TCAL).MethodsUsing whole-genome cDNA microarray technology (Illumina), we examined GE in nontransformed human cells after 4h exposure to DBPs at predetermined equipotent concentrations, identified significant changes in gene expression (p≤0.01), and investigated the relevance of these genes to specific toxicity pathways via gene and pathway enrichment analysis.ResultsGenes related to activation of oxidative stress-responsive pathways exhibited fewer alterations than expected based on prior work, whereas all DBPs induced notable effects on transcription of genes related to immunity and inflammation.DiscussionOur results suggest that alterations to genes associated with immune and inflammatory pathways play an important role in the potential adverse health effects of exposure to DBPs. The interrelationship between these pathways and the production of reactive oxygen species (ROS) may explain the common occurrence of oxidative stress in other studies exploring DBP toxicity. Finally, transcriptional changes and shared induction of toxicity pathways observed for all DBPs caution of additive effects of mixtures and suggest further assessment of adverse health effects of mixtures is warranted. https://doi.org/10.1289/EHP4945.
| S-EPMC6927499 | biostudies-literature
Project description:Glycation is a post-translational modification underlied by the interaction of protein amino and guanidino groups with carbonyl compounds like reducing sugars and α-dicarbonyls. In the first steps of this process, the protein amino groups react with reducing carbohydrates yielding the corresponding keto- and aldimines, i.e. Amadori and Heyns compounds, respectively. Further degradation of these products results in the formation of advanced glycation end products (AGEs). Alternatively, some representatives of this heterogeneous compound group can originate from α-dicarbonyl products of monosaccharide autoxidation or primary cellular metabolism. In mammals, AGEs are continuously formed during the life of the organism, and accumulate in the tissues, being well-known markers of ageing and impacting age-related stiffing of tissues, decrease of muscle performance, and atherosclerotic changes. However, although the role of AGEs in the ageing of animal tissues is well-studied, their impact in the age-related molecular alterations in plants is completely unknown. To fill this gap, we present here a comprehensive study of the age-related changes in the plant glycated proteome in terms of affected proteins and individual glycation sites therein. Thereby, we consider the qualitative and quantitative changes in glycation patterns in terms of the general metabolic background, pathways of AGE formation, and the status of plant anti-oxidative/anti-glycative defense. Although the patterns of glycated proteins were only minimally influenced by plant age, the abundances of 96 advanced glycation sites in 71 proteins were significantly affected in an age-dependent manner and clearly indicate the existence of glycation hotspots in the plant proteome, the nature of which is discussed here in the sense of structural considerations.
2017-06-19 | PXD006434 | Pride
Project description:Tendon pathologies affect a large portion of people with diabetes. This high rate of tendon pain, injury, and disease appears to manifest independent of well-controlled HbA1c and fasting blood glucose. Advanced glycation end products (AGEs) are elevated in the serum of those with diabetes. In vitro, AGEs severely impact tendon fibroblast proliferation and mitochondrial function. However, the extent that AGEs impact the tendon cell transcriptome has not been evaluated. The purpose of this study was to investigate transcriptome-wide changes that occur to tendon-derived fibroblasts following treatment with AGEs. We propose to complete a descriptive approach to pathway profiling to broaden our mechanistic understanding of cell signaling events that may contribute to the development of tendon pathology. Rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived AGEs (200μg/ml) for 48 hours in normal glucose (5.5mM) conditions. In addition, total RNA was isolated, and the PolyA+ library was sequenced. We demonstrate that tendon fibroblasts treated with 200μg/ml of AGEs differentially express 2,159 gene targets compared to fibroblasts treated with an equal amount of BSA-Control. Additionally, we report in a descriptive and ranked fashion 21 implicated cell-signaling pathways. We demonstrate that tendon fibroblasts treated with 200μg/ml of AGEs differentially express 2,159 gene targets compared to fibroblasts treated with an equal amount of BSA-Control. Additionally, we report in a descriptive and ranked fashion 21 implicated cell-signaling pathways. Our findings suggest that AGEs disrupt the tendon fibroblast transcriptome on a large scale and that these pathways may contribute to the development and progression of diabetic tendinopathy. Specifically, pathways related to cell cycle progression and extracellular matrix remodeling were affected in our data set and may play a contributing role in the development of diabetic tendon complications.
2022-05-27 | GSE204714 | GEO
Project description:The receptor for advanced glycation end products (RAGE) plays a key role in mammal physiology and in the etiology and progression of inflammatory and oxidative stress-based diseases. In adults, RAGE expression is high only in the lung where the protein concentrates in the basal membrane of Type I alveolar epithelial cells. In diseases, RAGE levels increase in the affected tissues and sustain chronic inflammation. RAGE exists as a single trans-membrane protein with an ectodomain and a short carboxyl-terminal tail essential for signaling, or also as a soluble ectodomain (sRAGE) that acts as a decoy receptor. The ectodomain is composed of a variable and two constant IgG-like domains (V, C1 and C2). VC1 is a single integrated unit responsible for binding of RAGE to the majority of its ligands including the advanced glycation End products (AGEs), S100 proteins and HMGB-1. Here, we report the identification of 20 new RAGE binding partners captured from human plasma and involved in the coagulation and complement processes and in the extracellular matrix. Four proteins contained a -carboxyl glutamic acid (Gla)-domain. Using MicroScale Thermophoresis, we quantified the interaction of prothrombin (PT) with VC1 and with sRAGE. Calcium competed in the binding of PT to sRAGE and PT devoid of the Gla-domain did not bind to sRAGE, providing evidence that the Gla-domain is critical for the interaction. Finally, the presence of VC1 delayed plasma clotting in a dose-dependent manner. We propose that RAGE is involved in modulating blood coagulation presumably in conditions of lung injury.
2020-07-14 | PXD020355 | Pride
Project description:This study was aimed to correlate the pre- and 6-month postpercutaneous coronary intervention (PCI) serum concentrations of advanced glycation end products (AGE), soluble receptors for advanced glycation end products (sRAGE), AGE/sRAGE ratio, and serum malondialdehyde (MDA) levels with in-stent restenosis (ISR) among patients receiving either a drug-eluting stent (DES) or a bare-metal stent (BMS).In-stent restenosis remains as an adverse outcome following PCI. Sixty consecutive nondiabetic, Caucasian male patients, diagnosed with a non-ST-elevation myocardial infarction who received either a DES or BMS via PCI, were enrolled. Baseline levels of serum AGE, sRAGE, AGE/sRAGE ratios, MDA, and angiographic parameters were determined at stenting and at 6 months. Patients with and without ISR at 6 months were compared on both baseline and 6-month biomarker levels and within stent types.The pre-PCI serum AGE levels and AGE/sRAGE ratios were higher in ISR patients compared with non-ISR patients, while the pre-PCI and post-PCI serum sRAGE levels were lower in ISR patients compared with non-ISR patients. The pre and post-PCI levels of MDA were also higher in ISR patients. Comparing stent types, relative levels of MDA between those with and without ISR at the respective time points were similar, although changes between time points appeared type specific.Post-PCI ISR correlates with low serum values of sRAGE and high serum values of AGE, MDA, and AGE/sRAGE ratio which are present at stenting. The associations of baseline AGE, sRAGE, AGE/sRAGE, and MDA levels with ISR appear consistent between stent types.
| S-EPMC6221796 | biostudies-literature