Transcriptome study of colon epithelial cells in Reg3a-transgenic mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64932 | GEO | 2018/01/31
REPOSITORIES: GEO
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Project description:Antimicrobial peptides (AMPs) serve key proposed roles in defending the urinary tract against invading uropathogens, but individual AMPs bearing greatest responsibility for these functions remain largely unknown. We identified RegIIIγ as the most transcriptionally upregulated AMP in bladder transcriptomes following uropathogenic Escherichia coli (UPEC) infection. We confirmed induction of RegIIIγ mRNA during cystitis and pyelonephritis by quantitative RT-PCR. Immunoblotting demonstrates increased bladder and urinary RegIIIγ protein levels following UPEC infection. Immunostaining localizes RegIIIγ protein to urothelial cells of infected bladders and kidneys. Human patients with cystitis and pyelonephritis exhibit increased urine levels of the orthologous HIP/PAP protein. Recombinant RegIIIγ protein does not demonstrate bactericidal activity toward UPEC in vitro, but does kill Staphylococcus saprophyticus in a dose-dependent manner. RegIIIγ knockout and control urinary tracts contain comparable bacterial burden following experimental inoculation of UPEC as well as Gram-positive uropathogens. Thus, while RegIIIγ and HIP/PAP expression occurs in human and murine UTI, their specific functions in the urinary tract remain uncertain.
2015-12-29 | GSE72007 | GEO
Project description:We employed HITS-CLIP to map genome wide Star-PAP mRNA binding and define the role of RBM10 on global Star-PAP mRNA association. We show a transcriptome-wide association of Star-PAP which is diminished on cellular Star-PAP depletion. HITs-CLIP data analysis of RBM10 knockdown and pulldown with anti Star-PAP antibody on HEK293 cells indicates significance of RBM10 in Star-PAP and mRNA association.
2021-08-25 | GSE182643 | GEO
Project description:At the base of the intestinal crypt, long-lived Lgr5+ stem cells are intercalated by Paneth cells that provide essential niche signals for stem-cell maintenance. This unique epithelial anatomy makes the intestinal crypt one of the most accessible models for the study of adult stem cell biology. The glycosylation patterns of this compartment are poorly characterized and the impact of glycans on stem cell differentiation remains largely unexplored. We found that Paneth cells, but not Lgr5+ stem cells, express abundant terminal N-acetyllactosamine (LacNAc). Employing an enzymatic method to edit glycans in cultured crypt organoids, we assessed the functional role of LacNAc in the intestinal crypt. We show that blocking access to LacNAc on Paneth cells leads to hyperproliferation of the neighbouring Lgr5+ stem cells, which is accompanied by the down-regulation of genes that are known as negative regulators of proliferation
2017-12-27 | GSE108512 | GEO
Project description:Objectives: Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. Methods: A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect intestinal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers – intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Results: The severity of OSA was related to differences in the structure and composition of the intestinal microbiome. Enriched Fusobacterium, Megamonasa, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the intestinal microbiome, intestinal barrier biomarkers, and AHI. Conclusions: The study confirms that changes in the intestinal microbiota are related to intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.
2023-08-30 | GSE181270 | GEO
Project description:The modification of galactose with α1,2-fucose is involved in symbiosis with intestinal bacteria and elimination of pathogenic bacteria. It is postulated that α1,2-fucosylated mucin secreted from goblet cells is involved in defending an organism against infections, but the detailed molecular mechanisms are yet to be elucidated. It was previously reported that Paneth cells of the small intestine were positive for UEA-1 lectin staining. However, glycoproteins in Paneth cells carrying α1,2-fucose have not yet been identified. Glycoproteomic analysis of ileal lysates identified 3212 O-linked and 2962 N-linked glycopeptides. In particular, cryptdin-related sequence 1 (CRS1) expressed in Paneth cells was found to be α1,2-fucosylated. Unlike other antimicrobial α-defensin proteins, CRS1 contains unique Thr residues, which are modified with O-glycans, with 3HexNAc2Hex1Fuc1NeuAc being the main glycoform. Identification of α1,2-fucose on the O-glycans of CRS1 expressed in Paneth cells will pave the way for a mechanistic understanding of α1,2-fucose-dependent symbiosis with intestinal bacteria and elimination of pathogenic bacteria in the intestine.
2020-11-05 | PXD022132 | JPOST Repository
Project description:Acute superior mesenteric vein thrombosis (ASMVT) decreases the expression of junction-associated proteins and the number of intestinal epithelial cells, which leads to intestinal epithelial barrier disruption. Thermoprotein deposition has also recently been identified as an important cause of mucosal barrier defects. However, the role and mechanism of thermoprotein deposition in asmvt is not fully understood. Differentially expressed microRNAs (miRNAs) in the intestinal tissues of ASMVT mice were detected by transcriptome sequencing (RNA-Seq). To identify miRNAs involved in intestinal barrier disruption, we performed RNA-Seq analysis of intestinal tissues from ASMVT mice . Sixty miRNAs were abnormally expressed in normal intestinal tissues compared with ASMVT-induced intestinal tissues.
2024-01-25 | GSE240523 | GEO
Project description:To assess the selectivity of SLC16A3/MCT4 inhibitor slCeMM1, we derived diazirine-alkyne photoaffinity probe (slCeMM1-PAP). We next used HAP1 and MDAMB231 cell lines for MS experiment, comparing the enrichment of proteins by slCeMM1-PAP and conditions where slCeMM1-PAP was competed with slCeMM1 or it’s structurally related inactive control (S1_007). We found that among proteins enriched by slCeMM1-PAP, only SLC16A3 was competed by slCeMM1, but not S1_007, confirming the SLC16A3 engagement by slCeMM1 and suggesting overall good selectivity of slCeMM1.
2023-10-16 | PXD040089 | Pride
Project description:Background and Objectives: Antibiotic (ABx) therapy is associated with an increased risk for Crohn´s Disease but the underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy in patients. The aim of the present study was to unravel whether this rise in PA may promote colitis development via detrimental effects on the large intestinal barrier. Design: Transwell experiments were used to assess the impact of high PA in ABx-treated patients or vancomycin/metronidazole (V/M)-treated mice on the epithelial barrier. Serine protease profiling was performed using LC-MS/MS analysis. The impact of high PA on the intestinal barrier in WT/IL10-/- mice and on colitis development in IL10-/- mice was investigated using V/M+/-oral serine protease inhibitor (AEBSF) treatment. Results: The ABx-induced high PA was found to be due to significantly increased levels of pancreatic proteases and to impair the epithelial barrier. In WT mice, the rise in PA caused a transient increase in intestinal permeability but did not affect susceptibility towards DSS-induced acute colitis. In IL10-/- mice, the rise in PA caused a lasting impairment of the intestinal barrier, which was associated with inflammatory activation of the large intestinal tissue. In the long term, the lasting increase in PA upon repeated V/M treatment aggravated colitis development in IL10-/-mice. Conclusion: High PA is a frequent adverse effect of ABx therapy which is detrimental to the large intestinal barrier and may contribute to the development of chronic inflammation in genetically susceptible individuals.
2018-05-11 | PXD007914 | Pride
Project description:Interventions: Probiotics Group:Bifidobacterium lactis M8;2:Intestinal antimicrobials
Primary outcome(s): Intestinal flora;Intestinal barrier function;Humoral immune function;cellular immune function
Study Design: Randomized parallel controlled trial
| 2678440 | ecrin-mdr-crc
Project description:Intestinal barrier leakage constitutes a potential therapeutic target for many inflammatory diseases and represents a disease progression marker during chronic viral infections. The causes of altered gut barrier remain, however, mostly unknown. By using murine infection with lymphocytic choriomeningitis virus we demonstrated that, in contrast to an acute viral strain, a persistent viral isolate led to long-term viral replication in hematopoietic and mesenchymal, but not epithelial (IEC), cells in the intestine. Viral persistence drove sustained intestinal epithelial barrier leakage, which was characterized by increased paracellular flux of small molecules and was associated with enhanced colitis susceptibility. IFN-I signaling caused tight junction dysregulation in IEC, promoted gut microbiome shifts and enhanced intestinal CD8 T cell responses. Notably, both IFN-I receptor blockade and CD8 T cell depletion prevented infection-induced barrier leakage. Our study demonstrated that infection with a virus that persistently replicated in intestinal mucosa increased epithelial barrier permeability, and revealed IFN-I and CD8 T cells as causative factors of intestinal leakage during chronic infections.
2020-08-26 | GSE155120 | GEO